10-71741862-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_022124.6(CDH23):c.4786C>T(p.Arg1596Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,610,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1596H) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.4786C>T | p.Arg1596Cys | missense_variant | 38/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.4786C>T | p.Arg1596Cys | missense_variant | 38/70 | 5 | NM_022124.6 | P1 | |
CDH23 | ENST00000398792.3 | n.1475C>T | non_coding_transcript_exon_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000291 AC: 7AN: 240566Hom.: 0 AF XY: 0.00000763 AC XY: 1AN XY: 131082
GnomAD4 exome AF: 0.0000425 AC: 62AN: 1458464Hom.: 1 Cov.: 33 AF XY: 0.0000441 AC XY: 32AN XY: 725250
GnomAD4 genome AF: 0.000131 AC: 20AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74384
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 11, 2015 | The p.Arg1596Cys variant in CDH23 has not been previously reported in individual s with hearing loss, but has been identified in 4/6868 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s372636295). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predi ction tools suggest that the variant may impact the protein, though this informa tion is not predictive enough to assume pathogenicity. In summary, the clinical significance of the p.Arg1596Cys variant is uncertain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at