rs773018940
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001481.3(GAS8):c.244C>T(p.Arg82Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,601,202 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82Q) has been classified as Likely benign.
Frequency
Consequence
NM_001481.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAS8 | NM_001481.3 | c.244C>T | p.Arg82Trp | missense_variant | 3/11 | ENST00000268699.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAS8 | ENST00000268699.9 | c.244C>T | p.Arg82Trp | missense_variant | 3/11 | 1 | NM_001481.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000999 AC: 22AN: 220224Hom.: 0 AF XY: 0.0000921 AC XY: 11AN XY: 119378
GnomAD4 exome AF: 0.0000476 AC: 69AN: 1448944Hom.: 0 Cov.: 32 AF XY: 0.0000514 AC XY: 37AN XY: 719762
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74446
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 33 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 82 of the GAS8 protein (p.Arg82Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GAS8-related conditions. ClinVar contains an entry for this variant (Variation ID: 571141). 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 C15"). 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