rs141216815
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000321117.10(DNMT3A):c.2151C>T(p.Asn717=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000914 in 1,614,262 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00093 ( 1 hom. )
Consequence
DNMT3A
ENST00000321117.10 synonymous
ENST00000321117.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.666
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 2-25240662-G-A is Benign according to our data. Variant chr2-25240662-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.666 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000735 (112/152370) while in subpopulation AMR AF= 0.00183 (28/15310). AF 95% confidence interval is 0.0013. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 112 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMT3A | NM_022552.5 | c.2151C>T | p.Asn717= | synonymous_variant | 18/23 | ENST00000321117.10 | NP_072046.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMT3A | ENST00000321117.10 | c.2151C>T | p.Asn717= | synonymous_variant | 18/23 | 1 | NM_022552.5 | ENSP00000324375 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000742 AC: 113AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000664 AC: 167AN: 251444Hom.: 0 AF XY: 0.000751 AC XY: 102AN XY: 135904
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GnomAD4 exome AF: 0.000932 AC: 1363AN: 1461892Hom.: 1 Cov.: 33 AF XY: 0.000952 AC XY: 692AN XY: 727246
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GnomAD4 genome AF: 0.000735 AC: 112AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.000711 AC XY: 53AN XY: 74514
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | DNMT3A: BP4, BP7, BS1 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 25, 2017 | - - |
DNMT3A-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Tatton-Brown-Rahman overgrowth syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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