rs200792658
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032119.4(ADGRV1):c.9440G>A(p.Arg3147Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,610,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R3147R) has been classified as Likely benign.
Frequency
Consequence
NM_032119.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.9440G>A | p.Arg3147Gln | missense_variant | 43/90 | ENST00000405460.9 | |
LOC105379077 | XR_001742802.2 | n.364-913C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.9440G>A | p.Arg3147Gln | missense_variant | 43/90 | 1 | NM_032119.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000362 AC: 55AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000302 AC: 75AN: 248466Hom.: 0 AF XY: 0.000297 AC XY: 40AN XY: 134858
GnomAD4 exome AF: 0.000218 AC: 318AN: 1458406Hom.: 0 Cov.: 29 AF XY: 0.000219 AC XY: 159AN XY: 725606
GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74442
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 24, 2017 | - - |
Usher syndrome type 2 Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Sharon lab, Hadassah-Hebrew University Medical Center | Jun 23, 2019 | - - |
Idiopathic generalized epilepsy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Paris Brain Institute, Inserm - ICM | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 04, 2020 | The p.Arg3147Gln variant in ADGRV1 (also known as GPR98) has been previously reported in 5 individuals with hearing loss (Neveling 2013, LMM data), 4 of whom also carried the p.Gly573Val variant of uncertain significance in ADGRV1. These two variants were determined to be in cis in 1 individual tested at our laboratory. The p.Arg3147Gln variant has also been reported in ClinVar (Variation ID # 46404) as of uncertain significance. It has also been identified in 0.1% (42/35316) of Latino chromosomes at a similar frequency as the p.Gly573Val variant (0.1%; 41/35348 Latino chromosomes) by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200792658 and dbSNP rs200789563). Collectively, these data suggest that these variants are in linkage disequilibrium and are in cis in all reported individuals identified thus far. Moreover, arginine (Arg) at position 3147 is not conserved in mammals or evolutionarily distant species. Of note, 2 mammals (Elephant and Opossum) carry a glutamine (Gln) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg3147Gln variant is uncertain. ACMG/AMP criteria applied: BS1_Supporting, BP4. - |
Febrile seizures, familial, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Institute of Human Genetics, University Hospital of Duesseldorf | - | - - |
Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at