rs201589645
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_022124.6(CDH23):c.3186C>A(p.Thr1062=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1062T) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.3186C>A | p.Thr1062= | synonymous_variant | 27/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.3186C>A | p.Thr1062= | synonymous_variant | 27/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.3186C>A | p.Thr1062= | synonymous_variant | 27/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000237 AC: 59AN: 248678Hom.: 0 AF XY: 0.000237 AC XY: 32AN XY: 135128
GnomAD4 exome AF: 0.000153 AC: 223AN: 1461604Hom.: 1 Cov.: 31 AF XY: 0.000155 AC XY: 113AN XY: 727088
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152340Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74490
ClinVar
Submissions by phenotype
CDH23-related disorder Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 07, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Usher syndrome type 1D Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Autosomal recessive nonsyndromic hearing loss 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2017 | p.Thr1062Thr in Exon 27 of CDH23: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.5% (46/10144) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org; dbSNP rs201589645). - |
Usher syndrome type 1 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 13, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at