NM_022124.6:c.3397G>T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_022124.6(CDH23):c.3397G>T(p.Glu1133*) variant causes a stop gained change. 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CDH23
NM_022124.6 stop_gained
NM_022124.6 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 5.24
Genes affected
CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-71724072-G-T is Pathogenic according to our data. Variant chr10-71724072-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2680515.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CDH23 | NM_022124.6 | c.3397G>T | p.Glu1133* | stop_gained | Exon 29 of 70 | ENST00000224721.12 | NP_071407.4 | |
| CDH23 | NM_001171930.2 | c.3397G>T | p.Glu1133* | stop_gained | Exon 29 of 32 | NP_001165401.1 | ||
| C10orf105 | NM_001168390.2 | c.-5-7730C>A | intron_variant | Intron 1 of 1 | NP_001161862.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1408096Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 695254
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1408096
Hom.:
Cov.:
32
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AC XY:
0
AN XY:
695254
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pituitary adenoma 5, multiple types Pathogenic:1
Nov 16, 2022
Baylor Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.