12-6841292-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002075.4(GNB3):c.5G>A(p.Gly2Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,284 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 (★★).
Frequency
Consequence
NM_002075.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 248854Hom.: 0 AF XY: 0.0000520 AC XY: 7AN XY: 134628
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461000Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 726708
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74446
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.5G>A (p.G2E) alteration is located in exon 3 (coding exon 1) of the GNB3 gene. This alteration results from a G to A substitution at nucleotide position 5, causing the glycine (G) at amino acid position 2 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. This variant has not been reported in the literature in individuals affected with GNB3-related conditions. This variant is present in population databases (rs782103240, gnomAD 0.04%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2 of the GNB3 protein (p.Gly2Glu). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at