rs2276598
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_022552.5(DNMT3A):c.1266G>A(p.Leu422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,612,420 control chromosomes in the GnomAD database, including 25,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 3635 hom., cov: 33)
Exomes 𝑓: 0.17 ( 21645 hom. )
Consequence
DNMT3A
NM_022552.5 synonymous
NM_022552.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.673
Genes affected
DNMT3A (HGNC:2978): (DNA methyltransferase 3 alpha) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 2-25246633-C-T is Benign according to our data. Variant chr2-25246633-C-T is described in ClinVar as [Benign]. Clinvar id is 1164958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.673 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.1266G>A | p.Leu422= | synonymous_variant | 10/23 | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.1266G>A | p.Leu422= | synonymous_variant | 10/23 | 1 | NM_022552.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.209 AC: 31799AN: 152058Hom.: 3622 Cov.: 33
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GnomAD3 exomes AF: 0.190 AC: 47115AN: 247968Hom.: 4890 AF XY: 0.183 AC XY: 24644AN XY: 134780
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GnomAD4 exome AF: 0.168 AC: 244632AN: 1460242Hom.: 21645 Cov.: 34 AF XY: 0.166 AC XY: 120277AN XY: 726354
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GnomAD4 genome ? AF: 0.209 AC: 31839AN: 152178Hom.: 3635 Cov.: 33 AF XY: 0.211 AC XY: 15714AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Tatton-Brown-Rahman overgrowth syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at