rs201890097
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000405460.9(ADGRV1):āc.16312A>Gā(p.Thr5438Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T5438I) has been classified as Likely benign.
Frequency
Consequence
ENST00000405460.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.16312A>G | p.Thr5438Ala | missense_variant | 76/90 | ENST00000405460.9 | NP_115495.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.16312A>G | p.Thr5438Ala | missense_variant | 76/90 | 1 | NM_032119.4 | ENSP00000384582 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000512 AC: 78AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000397 AC: 99AN: 249196Hom.: 0 AF XY: 0.000362 AC XY: 49AN XY: 135188
GnomAD4 exome AF: 0.00110 AC: 1604AN: 1461638Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 789AN XY: 727102
GnomAD4 genome AF: 0.000512 AC: 78AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74494
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 27, 2019 | This variant is associated with the following publications: (PMID: 22135276, 32707200) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 22, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 18, 2021 | - - |
Febrile seizures, familial, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 25, 2024 | - - |
Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
ADGRV1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 11, 2024 | The ADGRV1 c.16312A>G variant is predicted to result in the amino acid substitution p.Thr5438Ala. This variant was reported in an individual with uveitis (Table S2, Li et al. 2020. PubMed ID: 32707200) and in a patient with Usher syndrome (Table S3, Le Quesne Stabej et al. 2011. PubMed ID: 22135276). This variant is reported in 0.079% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 12, 2013 | Thr5438Ala in Exon 76 of GPR98: This variant is not expected to have clinical si gnificance because it is poorly conserved across species, with two primates (mar moset and squirrel monkey) having an Ala at this position, and computational too ls (amino acid conservation, AlignGVGD, PolyPhen2, and SIFT) do not suggest an i mpact to the protein. In addition, it has been previously reported in one study as a "neutral" variant due to its presence in 4/878 (0.48%) control chromosomes (Le Quesne Stabej 2012), and was also identified in 0.1% (5/8240) of European A merican chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu; dbSNP rs201890097). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at