12-6845637-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002075.4(GNB3):c.751C>T(p.Arg251Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,648 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002075.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251072Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135782
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461488Hom.: 2 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727060
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with GNB3-related conditions. This variant is present in population databases (rs782368057, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 251 of the GNB3 protein (p.Arg251Cys). 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at