rs150593932
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_153676.4(USH1C):c.2410G>A(p.Ala804Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,614,158 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. A804A) has been classified as Likely benign.
Frequency
Consequence
NM_153676.4 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 |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.2410G>A | p.Ala804Thr | missense_variant | 24/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.1510G>A | p.Ala504Thr | missense_variant | 19/21 | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2410G>A | p.Ala804Thr | missense_variant | 24/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.1510G>A | p.Ala504Thr | missense_variant | 19/21 | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152172Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000302 AC: 76AN: 251466Hom.: 1 AF XY: 0.000383 AC XY: 52AN XY: 135898
GnomAD4 exome AF: 0.000168 AC: 245AN: 1461868Hom.: 0 Cov.: 35 AF XY: 0.000226 AC XY: 164AN XY: 727234
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152290Hom.: 1 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74454
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 24, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2020 | See Variant Classification Assertion Criteria. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2014 | The Ala804Thr variant in USH1C has not been previously reported in individuals w ith hearing loss, but has been identified in 0.01% (1/8586) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; dbSNP rs150593932). Computational prediction tools and conservation analy ses do not provide strong support for or against an impact to the protein. In su mmary, the clinical significance of the Ala804Thr variant is uncertain. - |
Usher syndrome type 1C 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at