chr20-32780363-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006892.4(DNMT3B):c.40G>C(p.Ala14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A14A) has been classified as Likely benign.
Frequency
Consequence
NM_006892.4 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 |
---|---|---|---|---|---|---|---|
DNMT3B | NM_006892.4 | c.40G>C | p.Ala14Pro | missense_variant | 2/23 | ENST00000328111.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT3B | ENST00000328111.6 | c.40G>C | p.Ala14Pro | missense_variant | 2/23 | 1 | NM_006892.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251112Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135788
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461774Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727182
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74300
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 | Aug 23, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 14 of the DNMT3B protein (p.Ala14Pro). This variant is present in population databases (rs770859652, gnomAD 0.009%). 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: 1404403). 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: "Deleterious"; 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