rs371970388
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_032119.4(ADGRV1):c.13228G>A(p.Glu4410Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,600,272 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).
Frequency
Consequence
NM_032119.4 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 | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.13228G>A | p.Glu4410Lys | missense_variant | 65/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.13228G>A | p.Glu4410Lys | missense_variant | 65/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000638510.1 | n.495G>A | non_coding_transcript_exon_variant | 1/26 | 1 | ||||
ADGRV1 | ENST00000425867.3 | c.2182G>A | p.Glu728Lys | missense_variant | 13/38 | 5 | |||
ADGRV1 | ENST00000639431.1 | c.265+105366G>A | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000618 AC: 15AN: 242614Hom.: 0 AF XY: 0.0000304 AC XY: 4AN XY: 131364
GnomAD4 exome AF: 0.000123 AC: 178AN: 1448162Hom.: 0 Cov.: 30 AF XY: 0.000114 AC XY: 82AN XY: 717992
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 04, 2023 | Observed with the G2756R variant in the ADGRV1 gene in a patient with myoclonic epilepsy in published literature (Myers et al., 2018); Observed with the G2756R variant in the ADGRV1 gene in unrelated patients referred for genetic testing at GeneDx, confirmed to be on the same allele (in cis) in a single case; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29266188, 34160719, 36399868, 32962041) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 28, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Glu4410Lys va riant in GPR98 has not been previously reported in individuals with Usher syndro me, but has been identified in 3/61466 European chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs371970388). Altho ugh this variant has been seen in the general population, its frequency is not h igh enough to rule out a pathogenic role. The glutamic acid (Glu) at position 44 10 is not conserved across species with two mammals (squirrel and aardvark) havi ng a lysine (Lys) at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. In summary, while the clinical significance of the p.Glu4 410Lys variant is uncertain, available data suggest that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at