NM_032119.4:c.16874C>T
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_032119.4(ADGRV1):c.16874C>T(p.Ser5625Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00012 in 1,613,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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. S5625S) has been classified as Likely benign.
Frequency
Consequence
NM_032119.4 missense
Scores
Clinical Significance
Conservation
Publications
- Usher syndrome type 2Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Usher syndrome type 2CInheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- febrile seizures, familial, 4Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- nonsyndromic genetic hearing lossInheritance: AR Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152122Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000189 AC: 47AN: 248910 AF XY: 0.000296 show subpopulations
GnomAD4 exome AF: 0.000115 AC: 168AN: 1461142Hom.: 1 Cov.: 31 AF XY: 0.000182 AC XY: 132AN XY: 726746 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000171 AC: 26AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74438 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
ADGRV1: BP4 -
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not specified Uncertain:1
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ser5625Le u variant in GPR98 has not been previously reported in individuals with hearing loss or Usher syndrome, but has been identified in 0.13% (41/30734) of South Asi an chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadin stitute.org; dbSNP rs373862154). Although this variant has been seen in the gene ral population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis suggest that the p.Ser5 625Leu variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Ser5625Leu variant is uncertain. -
Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at