11-17501120-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_153676.4(USH1C):c.2311G>A(p.Gly771Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G771V) has been classified as Uncertain significance.
Frequency
Consequence
NM_153676.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.2311G>A | p.Gly771Ser | missense_variant | 23/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.1411G>A | p.Gly471Ser | missense_variant | 18/21 | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2311G>A | p.Gly771Ser | missense_variant | 23/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.1411G>A | p.Gly471Ser | missense_variant | 18/21 | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250726Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135578
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461714Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32AN XY: 727152
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 09, 2014 | The Gly771Ser variant in USH1C has not been previously reported in individuals w ith hearing loss and was absent from large population studies. Computational pre diction tools and conservation analyses do not provide strong support for or aga inst an impact to the protein. In summary, the clinical significance of the Gly7 71Ser variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 471 of the USH1C protein (p.Gly471Ser). This variant is present in population databases (rs727505083, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 179726). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Usher syndrome type 1C Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at