chr10-71646541-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022124.6(CDH23):c.1373C>T(p.Pro458Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P458P) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1373C>T | p.Pro458Leu | missense_variant | 14/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.1373C>T | p.Pro458Leu | missense_variant | 14/32 | ||
CDH23 | NM_001171931.2 | c.1373C>T | p.Pro458Leu | missense_variant | 14/26 | ||
CDH23 | NM_052836.4 | c.1373C>T | p.Pro458Leu | missense_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1373C>T | p.Pro458Leu | missense_variant | 14/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
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 | Mar 11, 2017 | The p.Pro458Leu variant in CDH23 has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational p rediction tools and conservation analysis suggest that the p.Pro458Leu variant m ay impact the protein, though this information is not predictive enough to deter mine pathogenicity. In summary, the clinical significance of the p.Pro458Leu var iant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at