10-71732118-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_022124.6(CDH23):c.3847G>A(p.Val1283Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,704 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 (★★). Synonymous variant affecting the same amino acid position (i.e. V1283V) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 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 |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.3847G>A | p.Val1283Met | missense_variant | 32/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.3847G>A | p.Val1283Met | missense_variant | 32/32 | ||
C10orf105 | NM_001168390.2 | c.-6+5610C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.3847G>A | p.Val1283Met | missense_variant | 32/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249250Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135234
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461704Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727134
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1283 of the CDH23 protein (p.Val1283Met). This variant is present in population databases (rs758413650, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 228481). 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: "Not Available"; Align-GVGD: "Class C15"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 30, 2014 | The p.Val1283Met variant in CDH23 has not been previously reported in individual s with hearing loss. This variant has been identified in 4/16602 of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org). Although this variant has been seen in the general population, its freq uency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analyses do not provide strong support for or against a n impact to the protein. In summary, the clinical significance of the p.Val1283M et variant is uncertain. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at