rs762185930
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006892.4(DNMT3B):c.143G>A(p.Gly48Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006892.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
DNMT3B | NM_006892.4 | c.143G>A | p.Gly48Asp | missense_variant, splice_region_variant | 3/23 | ENST00000328111.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3B | ENST00000328111.6 | c.143G>A | p.Gly48Asp | missense_variant, splice_region_variant | 3/23 | 1 | NM_006892.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251482Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135918
GnomAD4 exome AF: 0.000103 AC: 151AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.000111 AC XY: 81AN XY: 727234
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74272
ClinVar
Submissions by phenotype
Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 48 of the DNMT3B protein (p.Gly48Asp). This variant is present in population databases (rs762185930, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DNMT3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 574974). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at