rs764873763
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032119.4(ADGRV1):āc.9034A>Gā(p.Thr3012Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,602,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3012I) has been classified as Uncertain significance.
Frequency
Consequence
NM_032119.4 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 |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.9034A>G | p.Thr3012Ala | missense_variant | 41/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.9034A>G | p.Thr3012Ala | missense_variant | 41/90 | 1 | NM_032119.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000416 AC: 1AN: 240598Hom.: 0 AF XY: 0.00000767 AC XY: 1AN XY: 130328
GnomAD4 exome AF: 0.0000152 AC: 22AN: 1450888Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 10AN XY: 721090
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 24, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Thr3012Ala va riant in GPR98 has not been previously reported in individuals with hearing loss , but has been identified in 1/66294 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org). Although this variant has been seen in the general population, its frequency is not high enough to rule ou t a pathogenic role. The threonine (Thr) at position 3012 is not conserved thro ugh species, with 1 mammal (tenrec) having an alanine (Ala) at this position, su ggesting that variants at this position may be tolerated. Additional computation al prediction tools do not provide strong evidence for or against an impact to t he protein. In summary, while the clinical significance of the p.Thr3012Ala vari ant is uncertain, the lack of evolutionary conservation suggests that it is more likely to be benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2021 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 3012 of the ADGRV1 protein (p.Thr3012Ala). This variant is present in population databases (rs764873763, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 228728). 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"). 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