rs17123657
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006892.4(DNMT3B):c.1881C>T(p.Asp627=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,076 control chromosomes in the GnomAD database, including 1,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.054 ( 662 hom., cov: 32)
Exomes 𝑓: 0.0076 ( 692 hom. )
Consequence
DNMT3B
NM_006892.4 synonymous
NM_006892.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.532
Genes affected
DNMT3B (HGNC:2979): (DNA methyltransferase 3 beta) 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 which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 20-32800274-C-T is Benign according to our data. Variant chr20-32800274-C-T is described in ClinVar as [Benign]. Clinvar id is 338179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT3B | NM_006892.4 | c.1881C>T | p.Asp627= | synonymous_variant | 17/23 | ENST00000328111.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3B | ENST00000328111.6 | c.1881C>T | p.Asp627= | synonymous_variant | 17/23 | 1 | NM_006892.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0539 AC: 8203AN: 152072Hom.: 660 Cov.: 32
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GnomAD3 exomes AF: 0.0162 AC: 4067AN: 251494Hom.: 277 AF XY: 0.0126 AC XY: 1710AN XY: 135922
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GnomAD4 exome AF: 0.00757 AC: 11064AN: 1461884Hom.: 692 Cov.: 35 AF XY: 0.00691 AC XY: 5027AN XY: 727246
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GnomAD4 genome ? AF: 0.0540 AC: 8223AN: 152192Hom.: 662 Cov.: 32 AF XY: 0.0524 AC XY: 3901AN XY: 74404
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency-centromeric instability-facial anomalies syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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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
DS_DG_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at