rs397517884
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_153676.4(USH1C):c.908G>A(p.Arg303Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R303W) has been classified as Uncertain significance.
Frequency
Consequence
NM_153676.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.908G>A | p.Arg303Gln | missense_variant | 12/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.908G>A | p.Arg303Gln | missense_variant | 12/21 | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.908G>A | p.Arg303Gln | missense_variant | 12/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.908G>A | p.Arg303Gln | missense_variant | 12/21 | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000822 AC: 2AN: 243224Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132546
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460494Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 726556
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74330
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 | Oct 26, 2010 | Variant classified as Uncertain Significance - Favor Benign. The Arg303Gln varia nt in USH1C has not been reported in the literature nor previously identified by our laboratory. The Arg303 residue is conserved across mammals though not in lo wer species and computational analyses (PolyPhen, SIFT, AlignGVGD) do not sugges t a high likelihood of impact to the protein. However, this information is not p redictive enough to rule out pathogenicity. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 09, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 303 of the USH1C protein (p.Arg303Gln). This variant is present in population databases (rs397517884, gnomAD 0.005%). 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: 48026). 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: "Tolerated"; PolyPhen-2: "Possibly 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