DNMT3A (Q9Y6K1) variants and mutations
DNMT3A (also known as Q9Y6K1) is a human protein-coding gene encoding a DNA (cytosine-5)-methyltransferase 3A protein. It establishes new DNA methylation patterns during development and hematopoietic differentiation. Somatic variants are common in clonal hematopoiesis and acute myeloid leukemia, while germline variants cause Tatton-Brown-Rahman overgrowth syndrome. This analysis covers 2,408 DNMT3A variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes acute myeloid leukemia, Tatton-Brown-Rahman overgrowth syndrome, and Heyn-Sproul-Jackson syndrome. Example DNMT3A variants include P2L, P2S, and A3D.
Variant analysis overview
- Gene: DNMT3A
- Protein: Q9Y6K1
- UniProt accession: Q9Y6K1
- Organism: Homo sapiens
- Variants analyzed: 2408
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,163 unspecified-consequence records; 131 frameshift variants; 1 stop retained variant; 47 synonymous variants; 41 missense variants; 10 in-frame deletions; 2 protein altering variant; 1 in-frame insertions; 7 stop-gained variants; 2 splice-region variants; 3 substitution
- Prediction scores: 1,796 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acute myeloid leukemia, Tatton-Brown-Rahman overgrowth syndrome, Heyn-Sproul-Jackson syndrome, myelodysplastic syndrome, myeloid leukemia, chronic myelomonocytic leukemia, ebv-positive nodal t- and nk-cell lymphoma, myelodysplastic syndrome with excess blasts, neoplasm, myeloproliferative disorder, hereditary disease, anemia.
Protein structure and variant hotspots
- Protein features: 3 domains; 4 binding sites; 10 post-translational modification sites.
- Structural context: 1,471 variants have structural context.
- PTM context: 20 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable DNMT3A variants
Examples include P2L, P2S, A3D, A3P, A3S, A3T, A3V, M4I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), cosmic curated COSV53076, REVEL 0.47, MetaLR 0.71
- P2S (p.Pro2Ser), Ensembl rs2149429172, REVEL 0.44, MetaLR 0.72
- A3D (p.Ala3Asp), Ensembl rs2034259976, REVEL 0.45, MetaLR 0.65
- A3P (p.Ala3Pro), ExAC rs745380962, TOPMed rs745380962, gnomAD rs745380962, Likely pathogenic
- A3S (p.Ala3Ser), rs745380962, ClinGen CA346254529, ClinVar RCV000984105, ExAC rs745380962, REVEL 0.24, MetaLR 0.50, Likely pathogenic, Multiple myeloma
- A3T (p.Ala3Thr), rs745380962, ClinGen CA1556578, ClinVar RCV002633926, ClinVar RCV003984337, REVEL 0.24, MetaLR 0.47, Uncertain significance, Inborn genetic diseases
- A3V (p.Ala3Val), Ensembl rs2034259976, REVEL 0.34, MetaLR 0.52
- M4I (p.Met4Ile), rs1457508951, gnomAD rs1457508951, ClinGen CA346254519, ClinVar RCV001755679, REVEL 0.53, MetaLR 0.75, Uncertain significance, not provided
- M4L (p.Met4Leu), Ensembl rs2149429139, REVEL 0.55, MetaLR 0.67
- P5S (p.Pro5Ser), rs1364437125, ClinGen CA346254514, ClinVar RCV003747657, gnomAD rs1364437125, REVEL 0.57, MetaLR 0.80, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- S6A (p.Ser6Ala), rs773893946, ClinGen CA1556577, ClinVar RCV000949244, ClinVar RCV001545677, REVEL 0.20, MetaLR 0.56, Likely benign, Inborn genetic diseases; Tatton-Brown-Rahman overgrowth syndrome; not provided
- S7G (p.Ser7Gly), rs770554124, ClinGen CA1556576, ClinVar RCV002720937, ExAC rs770554124, REVEL 0.23, MetaLR 0.60, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- S7T (p.Ser7Thr), Ensembl rs2149429109, MetaLR 0.63, MetaSVM -0.12
- G8D (p.Gly8Asp), Ensembl rs2149429095, REVEL 0.56, MetaLR 0.80
- G8S (p.Gly8Ser), ExAC rs781229619, TOPMed rs781229619, gnomAD rs781229619, REVEL 0.56, MetaLR 0.80
- G8V (p.Gly8Val), cosmic curated COSV10878, REVEL 0.57, MetaLR 0.80
- P9L (p.Pro9Leu), TOPMed rs1251105887, gnomAD rs1251105887, REVEL 0.30, MetaLR 0.58
- G10E (p.Gly10Glu), gnomAD rs2034258253, REVEL 0.25, MetaLR 0.50
- G10R (p.Gly10Arg), cosmic curated COSV10806, ExAC rs752093845, TOPMed rs752093845, gnomAD rs752093845, REVEL 0.23, MetaLR 0.49, Likely benign, not provided; Tatton-Brown-Rahman overgrowth syndrome
- D11A (p.Asp11Ala), cosmic curated COSV53073
- D11E (p.Asp11Glu), cosmic curated COSV53069, REVEL 0.37, MetaLR 0.77
- D11H (p.Asp11His), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D11N (p.Asp11Asn), TOPMed rs2034257910, REVEL 0.29, MetaLR 0.81, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- T12H (p.Thr12His), NCI-TCGA TCGA novel, MetaLR 0.51, MetaSVM -0.28, Variant assessed as somatic; high impact.
- T12I (p.Thr12Ile), TOPMed rs1013949923, gnomAD rs1013949923, REVEL 0.24, MetaLR 0.51
- T12S (p.Thr12Ser), TOPMed rs1013949923, gnomAD rs1013949923, REVEL 0.26, MetaLR 0.46
- S13N (p.Ser13Asn), TOPMed rs2034257512, REVEL 0.32, MetaLR 0.55
- S14G (p.Ser14Gly), gnomAD rs1373614770, REVEL 0.16, MetaLR 0.54
- A16T (p.Ala16Thr), Ensembl rs2149429027
- A17G (p.Ala17Gly), TOPMed rs1299885148, gnomAD rs1299885148, MetaLR 0.52, MetaSVM -0.50, Uncertain significance
- A17S (p.Ala17Ser), NCI-TCGA TCGA novel, REVEL 0.26, MetaLR 0.57, Variant assessed as somatic; moderate impact.
- A17V (p.Ala17Val), rs1299885148, ClinGen CA346254365, ClinVar RCV002598914, TOPMed rs1299885148, REVEL 0.31, MetaLR 0.54, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- R19G (p.Arg19Gly), 1000Genomes rs959218576, TOPMed rs959218576, gnomAD rs959218576, REVEL 0.49, MetaLR 0.74, Uncertain significance
- R19Q (p.Arg19Gln), TOPMed rs1290646331, gnomAD rs1290646331, REVEL 0.36, MetaLR 0.76, Uncertain significance, Intellectual disability
- R19W (p.Arg19Trp), rs959218576, ClinGen CA44279227, cosmic curated COSV53037, ClinVar RCV002644415, REVEL 0.54, MetaLR 0.74, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome; not provided
- E20K (p.Glu20Lys), rs781254365, ClinGen CA44279226, cosmic curated COSV53080, ClinVar RCV000997084, REVEL 0.27, MetaLR 0.49, Conflicting interpretations, not provided; Craniosynostosis syndrome; Tatton-Brown-Rahman overgrowth syndrome
- E21G (p.Glu21Gly), TOPMed rs1360086489, gnomAD rs1360086489, REVEL 0.27, MetaLR 0.59
- E21K (p.Glu21Lys), cosmic curated COSV53077, CADD 16.40, SIFT 0.60
- D22G (p.Asp22Gly), cosmic curated COSV53076, REVEL 0.22, MetaLR 0.58
- D22N (p.Asp22Asn), rs1351253637, ClinGen CA346254309, ClinVar RCV001768222, TOPMed rs1351253637, AlphaMissense 0.08, MetaLR 0.61, Uncertain significance, not provided
- R23* (p.Arg23Ter), rs2034255903, ClinGen CA346254291, ClinVar RCV001262399, Ensembl rs2034255903, Likely benign
- R23P (p.Arg23Pro), gnomAD rs1174462913, REVEL 0.43, MetaLR 0.76, Uncertain significance
- R23Q (p.Arg23Gln), rs1174462913, ClinGen CA346254286, cosmic curated COSV10458, ClinVar RCV002756282, REVEL 0.32, MetaLR 0.75, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome; Acute myeloid leukemia
- K24T (p.Lys24Thr), rs2466004588, ClinGen CA346254278, ClinVar RCV003404624, Uncertain significance, DNMT3A-related disorder
- D25=, rs538820253, NCI-TCGA Cosmic COSV5306, NCI-TCGA Cosmic COSV5308, AlphaMissense 0.06, MetaLR 0.34, Variant assessed as somatic; low impact.
- D25E (p.Asp25Glu), cosmic curated COSV53083, 1000Genomes rs538820253, ExAC rs538820253, TOPMed rs538820253, REVEL 0.23, MetaLR 0.34, Likely benign
- D25V (p.Asp25Val), gnomAD rs1477239833, REVEL 0.34, MetaLR 0.58
- G26* (p.Gly26Ter), cosmic curated COSV53055
- G26R (p.Gly26Arg), rs781524740, ClinGen CA1556554, ClinVar RCV001548200, ClinVar RCV003584975, REVEL 0.42, MetaLR 0.65, Conflicting interpretations, Tatton-Brown-Rahman overgrowth syndrome; not provided
- G26V (p.Gly26Val), cosmic curated COSV53055, REVEL 0.36, MetaLR 0.62
- E27* (p.Glu27Ter), NCI-TCGA Cosmic COSV5304, cosmic curated COSV53049, Variant assessed as somatic; high impact.
- E28* (p.Glu28Ter), cosmic curated COSV53073, CADD 38.00
- E28K (p.Glu28Lys), cosmic curated COSV10636, gnomAD rs1440279401, REVEL 0.44, MetaLR 0.80
- E30A (p.Glu30Ala), rs143730975, ClinGen CA158306, cosmic curated COSV53049, ClinVar RCV000120651, REVEL 0.50, MetaLR 0.74, Benign/Likely benign, Tatton-Brown-Rahman overgrowth syndrome; not provided
- E30D (p.Glu30Asp), Ensembl rs2149405333, MetaLR 0.81, MetaSVM 0.94
- E30G (p.Glu30Gly), rs143730975, ClinGen CA346251761, ClinVar RCV003746254, ClinVar RCV005240871, REVEL 0.53, MetaLR 0.80, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome; not specified
- E31A (p.Glu31Ala), ExAC rs747483936, gnomAD rs747483936, MetaLR 0.78, MetaSVM 0.62
- P32L (p.Pro32Leu), rs1200194867, ClinGen CA346251745, cosmic curated COSV10510, ClinVar RCV003407176, REVEL 0.17, MetaLR 0.50, Uncertain significance, not provided
- P32S (p.Pro32Ser), Ensembl rs2149405318, REVEL 0.18, MetaLR 0.39
- R33C (p.Arg33Cys), rs758534627, ClinGen CA1556551, cosmic curated COSV53044, ClinVar RCV003747455, REVEL 0.44, MetaLR 0.74, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- R33G (p.Arg33Gly), ExAC rs758534627, TOPMed rs758534627, gnomAD rs758534627, Uncertain significance
- R33H (p.Arg33His), rs746009417, ClinGen CA1556550, NCI-TCGA Cosmic COSV5304, cosmic curated COSV53049, REVEL 0.30, MetaLR 0.73, Uncertain significance, not provided; Tatton-Brown-Rahman overgrowth syndrome
- R33L (p.Arg33Leu), cosmic curated COSV53053, REVEL 0.43, MetaLR 0.66
- G34D (p.Gly34Asp), TOPMed rs1317444748, gnomAD rs1317444748, REVEL 0.35, MetaLR 0.63
- K35R (p.Lys35Arg), gnomAD rs2033350122, REVEL 0.22, MetaLR 0.54
- E36K (p.Glu36Lys), cosmic curated COSV10586, REVEL 0.50, MetaLR 0.78
- E37D (p.Glu37Asp), NCI-TCGA TCGA novel, MetaLR 0.82, MetaSVM 0.89, Variant assessed as somatic; moderate impact.
- R38C (p.Arg38Cys), rs779208522, ClinGen CA1556549, cosmic curated COSV99065, ClinVar RCV003584095, REVEL 0.49, MetaLR 0.78, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- R38H (p.Arg38His), rs369618387, ClinGen CA1556548, cosmic curated COSV53038, ClinVar RCV001837416, REVEL 0.36, MetaLR 0.77, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- R38L (p.Arg38Leu), rs369618387, ClinGen CA346251707, ClinVar RCV002957751, ESP rs369618387, REVEL 0.45, MetaLR 0.77, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- Q39* (p.Gln39Ter), cosmic curated COSV53053
- E40D (p.Glu40Asp), rs202118149, ClinGen CA346251691, ClinVar RCV003585552, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- E40K (p.Glu40Lys), cosmic curated COSV10586
- E40V (p.Glu40Val), Ensembl rs2149405247, MetaLR 0.72, MetaSVM 0.62
- P41L (p.Pro41Leu), rs1398341368, ClinGen CA346251685, ClinVar RCV001246960, TOPMed rs1398341368, AlphaMissense 0.07, MetaLR 0.61, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- P41S (p.Pro41Ser), gnomAD rs1391800442, REVEL 0.14, MetaLR 0.53
- S42G (p.Ser42Gly), gnomAD rs1465039597, REVEL 0.15, MetaLR 0.53
- S42N (p.Ser42Asn), Ensembl rs2149405210, REVEL 0.29, MetaLR 0.63
- T43I (p.Thr43Ile), rs1417961680, ClinGen CA346251671, ClinVar RCV003091713, TOPMed rs1417961680, REVEL 0.30, MetaLR 0.72, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- T43S (p.Thr43Ser), TOPMed rs1417961680, gnomAD rs1417961680, REVEL 0.27, MetaLR 0.65, Uncertain significance
- T44M (p.Thr44Met), rs199643287, ClinGen CA158313, cosmic curated COSV53054, ClinVar RCV000120652, REVEL 0.17, MetaLR 0.58, Likely benign, Inborn genetic diseases; Tatton-Brown-Rahman overgrowth syndrome
- A45S (p.Ala45Ser), cosmic curated COSV10586, MetaLR 0.55, MetaSVM -0.30
- A45T (p.Ala45Thr), Ensembl rs2149405178, REVEL 0.14, MetaLR 0.47
- A45V (p.Ala45Val), cosmic curated COSV53054, REVEL 0.24, MetaLR 0.46
- R46L (p.Arg46Leu), Ensembl rs1573454800, MetaLR 0.82, MetaSVM 0.69, Uncertain significance
- R46Q (p.Arg46Gln), rs1573454800, ClinGen CA346251655, NCI-TCGA Cosmic COSV5308, cosmic curated COSV53083, REVEL 0.41, MetaLR 0.84, Uncertain significance, not provided
- R46W (p.Arg46Trp), cosmic curated COSV53070, TOPMed rs1367571644, gnomAD rs1367571644, REVEL 0.63, MetaLR 0.82
- V48E (p.Val48Glu), TOPMed rs1468737197
- V48G (p.Val48Gly), cosmic curated COSV53056, TOPMed rs1468737197, REVEL 0.61, MetaLR 0.81
- G49R (p.Gly49Arg), TOPMed rs2033347077
- R50G (p.Arg50Gly), gnomAD rs1438813586, Uncertain significance
- R50L (p.Arg50Leu), cosmic curated COSV53039, MetaLR 0.81, MetaSVM 0.52
- R50Q (p.Arg50Gln), rs2149405135, ClinGen CA346251632, cosmic curated COSV10439, ClinVar RCV001840896, REVEL 0.36, MetaLR 0.82, Uncertain significance, not provided
- R50W (p.Arg50Trp), rs1438813586, ClinGen CA346251633, cosmic curated COSV10941, ClinVar RCV002471932, REVEL 0.51, MetaLR 0.81, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- P51A (p.Pro51Ala), TOPMed rs2033346523
- P51S (p.Pro51Ser), TOPMed rs2033346523
- P51T (p.Pro51Thr), TOPMed rs2033346523
- G52R (p.Gly52Arg), NCI-TCGA TCGA novel, REVEL 0.56, MetaLR 0.82, Variant assessed as somatic; moderate impact.
- G52W (p.Gly52Trp), Ensembl rs2149405109
- R53K (p.Arg53Lys), cosmic curated COSV10510, MetaLR 0.84, MetaSVM 0.76, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- K54N (p.Lys54Asn), cosmic curated COSV53083
- K54R (p.Lys54Arg), Ensembl rs2033346106
- K54T (p.Lys54Thr), cosmic curated COSV53084, MetaLR 0.82, MetaSVM 0.73
- R55C (p.Arg55Cys), rs2149405082, ClinGen CA346251600, NCI-TCGA Cosmic COSV5307, cosmic curated COSV53078, AlphaMissense 0.77, MetaLR 0.87, Uncertain significance, not provided
- R55H (p.Arg55His), rs1457666600, ClinGen CA346251599, NCI-TCGA Cosmic COSV9926, cosmic curated COSV99262, REVEL 0.48, MetaLR 0.87, Uncertain significance, DNMT3A-related disorder; Tatton-Brown-Rahman overgrowth syndrome
- K56E (p.Lys56Glu), Ensembl rs2149405073
- K56N (p.Lys56Asn), cosmic curated COSV53042, MetaLR 0.84, MetaSVM 0.95
- H57D (p.His57Asp), TOPMed rs1273917027, gnomAD rs1273917027
- H57P (p.His57Pro), Ensembl rs1573454732, MetaLR 0.78, MetaSVM 0.72
- H57Q (p.His57Gln), ESP rs139047498, ExAC rs139047498, TOPMed rs139047498, gnomAD rs139047498, REVEL 0.56, MetaLR 0.71
- H57Y (p.His57Tyr), TOPMed rs1273917027, gnomAD rs1273917027, REVEL 0.53, MetaLR 0.79
- P58F (p.Pro58Phe), cosmic curated COSV10510
- P58L (p.Pro58Leu), cosmic curated COSV53053, MetaLR 0.77, MetaSVM 0.66
- P59=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- P59L (p.Pro59Leu), cosmic curated COSV53040, ExAC rs772542252, TOPMed rs772542252, gnomAD rs772542252, REVEL 0.23, MetaLR 0.43, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- P59R (p.Pro59Arg), NCI-TCGA Cosmic COSV5304, REVEL 0.25, MetaLR 0.55, Variant assessed as somatic; high impact.
- P59S (p.Pro59Ser), cosmic curated COSV53070, MetaLR 0.55, MetaSVM -0.02, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- V60G (p.Val60Gly), Ensembl rs2149379621, MetaLR 0.86, MetaSVM 0.88
- E61* (p.Glu61Ter), Ensembl rs2149379615
- S62N (p.Ser62Asn), rs2465823184, ClinGen CA346084195, ClinVar RCV002572791, REVEL 0.27, MetaLR 0.63, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- S62R (p.Ser62Arg), cosmic curated COSV53068, REVEL 0.43, MetaLR 0.79, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- G63C (p.Gly63Cys), cosmic curated COSV10605
- G63S (p.Gly63Ser), rs781108426, ClinGen CA1556517, ClinVar RCV002547289, ClinVar RCV003886459, REVEL 0.24, MetaLR 0.37, Benign/Likely benign, Tatton-Brown-Rahman overgrowth syndrome; not provided
- D64A (p.Asp64Ala), cosmic curated COSV53053
- D64G (p.Asp64Gly), Ensembl rs2149379596, MetaLR 0.75, MetaSVM 0.69
- T65A (p.Thr65Ala), cosmic curated COSV10959, REVEL 0.25, MetaLR 0.67
- T65K (p.Thr65Lys), ExAC rs778149141, TOPMed rs778149141, gnomAD rs778149141, REVEL 0.43, MetaLR 0.74, Uncertain significance
- T65M (p.Thr65Met), rs778149141, ClinGen CA1556512, cosmic curated COSV10586, ClinVar RCV003747415, REVEL 0.34, MetaLR 0.74, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- T65R (p.Thr65Arg), ExAC rs778149141, TOPMed rs778149141, gnomAD rs778149141, REVEL 0.50, MetaLR 0.75, Uncertain significance
- P66L (p.Pro66Leu), cosmic curated COSV10510, MetaLR 0.75, MetaSVM 0.58
- D68E (p.Asp68Glu), Ensembl rs2149379562
- D68G (p.Asp68Gly), rs2465823019, ClinGen CA346084157, ClinVar RCV003223015, Uncertain significance, not provided
- D68Y (p.Asp68Tyr), ExAC rs756237176, gnomAD rs756237176, REVEL 0.48, MetaLR 0.79
- P69L (p.Pro69Leu), rs2031976051, ClinGen CA346084148, ClinVar RCV002305936, TOPMed rs2031976051, REVEL 0.11, MetaLR 0.55, Uncertain significance, not provided
- P69R (p.Pro69Arg), TOPMed rs2031976051, MetaLR 0.56, MetaSVM -0.35, Uncertain significance
- A70T (p.Ala70Thr), gnomAD rs1284202162
- A70V (p.Ala70Val), rs746884153, ClinGen CA1556510, ClinVar RCV003072568, ClinVar RCV003427560, REVEL 0.15, MetaLR 0.64, Uncertain significance, not provided; Tatton-Brown-Rahman overgrowth syndrome
- V71M (p.Val71Met), Ensembl rs2149379531, REVEL 0.15, MetaLR 0.60
- I72S (p.Ile72Ser), Ensembl rs2149379527, MetaLR 0.49, MetaSVM -0.63
- S73A (p.Ser73Ala), ExAC rs758401672, gnomAD rs758401672
- S75C (p.Ser75Cys), NCI-TCGA Cosmic COSV5308, Variant assessed as somatic; moderate impact.
- S75F (p.Ser75Phe), cosmic curated COSV10959, ExAC rs750339895, gnomAD rs750339895, REVEL 0.22, MetaLR 0.63
- S75Y (p.Ser75Tyr), cosmic curated COSV53086, MetaLR 0.62, MetaSVM 0.17
- P76S (p.Pro76Ser), NCI-TCGA Cosmic COSV5307, cosmic curated COSV53077, MetaLR 0.50, MetaSVM -0.42, Variant assessed as somatic; moderate impact.
- S77F (p.Ser77Phe), rs2031973986, ClinGen CA346084102, ClinVar RCV001330537, Ensembl rs2031973986, REVEL 0.33, MetaLR 0.71, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- M78I (p.Met78Ile), cosmic curated COSV53084, MetaLR 0.49, MetaSVM -0.49
- M78T (p.Met78Thr), rs1558705159, ClinGen CA346084095, ClinVar RCV001759173, ClinVar RCV004980679, REVEL 0.21, MetaLR 0.52, Uncertain significance, not provided; Inborn genetic diseases; Tatton-Brown-Rahman overgrowth syndrome
- M78V (p.Met78Val), rs2465822722, ClinGen CA346084098, ClinVar RCV003034500, REVEL 0.19, MetaLR 0.51, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- A79S (p.Ala79Ser), ExAC rs765111399, gnomAD rs765111399, REVEL 0.33, MetaLR 0.74, Uncertain significance
- A79T (p.Ala79Thr), ExAC rs765111399, gnomAD rs765111399, REVEL 0.34, MetaLR 0.76, Uncertain significance, not provided
- A79V (p.Ala79Val), Ensembl rs2149379477, REVEL 0.36, MetaLR 0.76
- D81H (p.Asp81His), Ensembl rs2149379454
- D81N (p.Asp81Asn), Ensembl rs2149379454, MetaLR 0.73, MetaSVM 0.60
- S82* (p.Ser82Ter), Ensembl rs2149379444
- S82P (p.Ser82Pro), Ensembl rs1307202807
- G83D (p.Gly83Asp), rs2031972346, ClinGen CA346084059, cosmic curated COSV53069, ClinVar RCV002586123, REVEL 0.31, MetaLR 0.68, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- G83R (p.Gly83Arg), Ensembl rs2149379431
- G83S (p.Gly83Ser), Ensembl rs2149379431
- G83V (p.Gly83Val), cosmic curated COSV10439, REVEL 0.26, MetaLR 0.59
- A84P (p.Ala84Pro), ExAC rs753287419, TOPMed rs753287419, gnomAD rs753287419, Uncertain significance
- A84T (p.Ala84Thr), rs753287419, ClinGen CA1556504, cosmic curated COSV53080, ClinVar RCV002612626, REVEL 0.29, MetaLR 0.39, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- A84V (p.Ala84Val), ExAC rs763793247, gnomAD rs763793247, REVEL 0.28, MetaLR 0.52
- S85* (p.Ser85Ter), cosmic curated COSV10959, CADD 28.40
- S85L (p.Ser85Leu), cosmic curated COSV53038, Ensembl rs2149379393, MetaLR 0.42, MetaSVM -0.69
- S85P (p.Ser85Pro), ExAC rs760236260, gnomAD rs760236260, REVEL 0.36, MetaLR 0.51
- S85T (p.Ser85Thr), ExAC rs760236260, gnomAD rs760236260, REVEL 0.20, MetaLR 0.54
- E86K (p.Glu86Lys), gnomAD rs1413294518, REVEL 0.38, MetaLR 0.71
- E86Q (p.Glu86Gln), cosmic curated COSV53044, MetaLR 0.58, MetaSVM -0.25
- P89L (p.Pro89Leu), cosmic curated COSV53049, Ensembl rs2149379357
- P89R (p.Pro89Arg), cosmic curated COSV53068
- P89S (p.Pro89Ser), rs2031969934, ClinGen CA346084026, ClinVar RCV002279023, ClinVar RCV003746613, AlphaMissense 0.09, MetaLR 0.83, Uncertain significance, not provided; Tatton-Brown-Rahman overgrowth syndrome
- N90S (p.Asn90Ser), rs769476651, ClinGen CA1556499, ClinVar RCV002890795, ExAC rs769476651, REVEL 0.36, MetaLR 0.76, Uncertain significance, Tatton-Brown-Rahman overgrowth syndrome
- G91E (p.Gly91Glu), cosmic curated COSV53075
- D92E (p.Asp92Glu), cosmic curated COSV10959
- D92N (p.Asp92Asn), NCI-TCGA Cosmic COSV5305, cosmic curated COSV53051, Variant assessed as somatic; moderate impact.
- D92V (p.Asp92Val), Ensembl rs2149379328, MetaLR 0.76, MetaSVM 0.50
- E94Q (p.Glu94Gln), Ensembl rs2149379319, MetaLR 0.55, MetaSVM -0.30
- R96G (p.Arg96Gly), ExAC rs775033041, gnomAD rs775033041
- R96Q (p.Arg96Gln), rs771499883, ClinGen CA1556496, ClinVar RCV002022118, ClinVar RCV004746563, REVEL 0.28, MetaLR 0.62, Uncertain significance, Acute myeloid leukemia; Heyn-Sproul-Jackson syndrome; Tatton-Brown-Rahman overgr
- R96W (p.Arg96Trp), ExAC rs775033041, gnomAD rs775033041, REVEL 0.40, MetaLR 0.78
Public DNMT3A analysis runs
- DNMT3A analysis run — DNMT3A (2,408 variants) — completed 2026-08-18