chr5-90628828-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_032119.4(ADGRV1):c.1505C>T(p.Ala502Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,434 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A502E) has been classified as Uncertain significance.
Frequency
Consequence
NM_032119.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.1505C>T | p.Ala502Val | missense_variant | 8/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.1505C>T | p.Ala502Val | missense_variant | 8/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000504142.2 | n.271C>T | non_coding_transcript_exon_variant | 2/14 | 5 | ||||
ADGRV1 | ENST00000640083.1 | n.1210C>T | non_coding_transcript_exon_variant | 6/6 | 5 | ||||
ADGRV1 | ENST00000640109.1 | n.1601C>T | non_coding_transcript_exon_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247994Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134504
GnomAD4 exome AF: 0.0000459 AC: 67AN: 1461256Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38AN XY: 726868
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 26, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Ala502Val varia nt in GPR98 has not been reported in the literature nor previously identified by our laboratory but has been identified in 1/6702 (0.01%) European American chro mosomes from a broad, though clinically unspecified population (NHLBI Exome Sequ encing Project; http://evs.gs.washington.edu/EVS). Computational analyses (bioch emical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugg est that the Ala502Val variant may not impact the protein, though this informati on is not predictive enough to rule out pathogenicity. The presence of this vari ant in an individual with another likely explanation for hearing loss decreases the likelihood that the Ala502Val variant is pathogenic. In summary, the clinica l significance of this variant cannot be determined with certainty; however base d upon the computation predictions, presence in the general population and alter nate explanation for hearing loss, we would lean towards a more likely benign ro le. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 15, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at