2-25246764-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM1PP3BS2_Supporting
The NM_022552.5(DNMT3A):c.1135C>T(p.Arg379Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R379R) has been classified as Likely benign.
Frequency
Consequence
NM_022552.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.1135C>T | p.Arg379Cys | missense_variant | 10/23 | ENST00000321117.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.1135C>T | p.Arg379Cys | missense_variant | 10/23 | 1 | NM_022552.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461112Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726896
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74500
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 14, 2016 | - - |
DNMT3A-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 31, 2023 | The DNMT3A c.1135C>T variant is predicted to result in the amino acid substitution p.Arg379Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00078% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-25469633-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at