12-6841608-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002075.4(GNB3):c.80A>G(p.Asp27Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D27D) has been classified as Benign.
Frequency
Consequence
NM_002075.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNB3 | NM_002075.4 | c.80A>G | p.Asp27Gly | missense_variant | 3/10 | ENST00000229264.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNB3 | ENST00000229264.8 | c.80A>G | p.Asp27Gly | missense_variant | 3/10 | 5 | NM_002075.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461372Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726966
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74244
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | 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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 960328). This variant has not been reported in the literature in individuals affected with GNB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 27 of the GNB3 protein (p.Asp27Gly). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at