chr10-71677578-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_022124.6(CDH23):c.1637G>T(p.Arg546Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,457,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1637G>T | p.Arg546Leu | missense_variant | Exon 16 of 70 | ENST00000224721.12 | NP_071407.4 | |
CDH23 | NM_001171930.2 | c.1637G>T | p.Arg546Leu | missense_variant | Exon 16 of 32 | NP_001165401.1 | ||
CDH23 | NM_001171931.2 | c.1637G>T | p.Arg546Leu | missense_variant | Exon 16 of 26 | NP_001165402.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000414 AC: 10AN: 241258Hom.: 0 AF XY: 0.0000611 AC XY: 8AN XY: 130950
GnomAD4 exome AF: 0.0000316 AC: 46AN: 1457920Hom.: 0 Cov.: 31 AF XY: 0.0000442 AC XY: 32AN XY: 724736
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 546 of the CDH23 protein (p.Arg546Leu). This variant is present in population databases (rs199508694, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at