chr10-71645875-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_022124.6(CDH23):​c.1185C>T​(p.Ser395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,613,460 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.106
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 10-71645875-C-T is Benign according to our data. Variant chr10-71645875-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 45863.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR,Digenic gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH23NM_022124.6 linkuse as main transcriptc.1185C>T p.Ser395= synonymous_variant 13/70 ENST00000224721.12
CDH23NM_001171930.2 linkuse as main transcriptc.1185C>T p.Ser395= synonymous_variant 13/32
CDH23NM_001171931.2 linkuse as main transcriptc.1185C>T p.Ser395= synonymous_variant 13/26
CDH23NM_052836.4 linkuse as main transcriptc.1185C>T p.Ser395= synonymous_variant 13/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH23ENST00000224721.12 linkuse as main transcriptc.1185C>T p.Ser395= synonymous_variant 13/705 NM_022124.6 P1Q9H251-1

Frequencies

GnomAD3 genomes
AF:
0.000591
AC:
90
AN:
152208
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00188
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000173
AC:
43
AN:
248846
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135018
show subpopulations
Gnomad AFR exome
AF:
0.00155
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000709
Gnomad OTH exome
AF:
0.000828
GnomAD4 exome
AF:
0.000114
AC:
167
AN:
1461134
Hom.:
2
Cov.:
32
AF XY:
0.000125
AC XY:
91
AN XY:
726730
show subpopulations
Gnomad4 AFR exome
AF:
0.00221
Gnomad4 AMR exome
AF:
0.000269
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.000563
GnomAD4 genome
AF:
0.000611
AC:
93
AN:
152326
Hom.:
0
Cov.:
33
AF XY:
0.000604
AC XY:
45
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00195
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000307
Hom.:
0
Bravo
AF:
0.000831
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022CDH23: BP4, BP7 -
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Nov 11, 2016- -
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 11, 2020This variant is associated with the following publications: (PMID: 18429043) -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineJul 07, 2011p.Ser395Ser in exon 13 of CDH23: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located near a splice junction and has been identified in 0.2% (19/9594) of African chromoso mes by the Exome Aggregation Consortium (http://exac.broadinstitute.org/variant/ ; rs185105210). In addition, this variant is listed as presumed neutral in one publication (Oshima 2008). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
13
DANN
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs185105210; hg19: chr10-73405632; API