10-71439838-C-T

Position:

chr10-71439838-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022124.6(CDH23):c.7C>T(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,563,838 control chromosomes in the GnomAD database, including 5,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2655 hom., cov: 33)

Exomes 𝑓: 0.032 ( 2723 hom. )

Consequence

CDH23
NM_022124.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -0.134

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]

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00406006).

BP6

Variant 10-71439838-C-T is Benign according to our data. Variant chr10-71439838-C-T is described in ClinVar as [Benign]. Clinvar id is 46042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71439838-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	2/70	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	2/70	5	NM_022124.6	ENSP00000224721	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17618

AN:

151998

Hom.:

2644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0567

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0240

Gnomad OTH

AF:

0.0945

GnomAD3 exomes

AF:

0.0455

AC:

8039

AN:

176796

Hom.:

734

AF XY:

0.0417

AC XY:

3928

AN XY:

94102

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.0356

Gnomad EAS exome

AF:

0.00101

Gnomad SAS exome

AF:

0.0486

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0321

AC:

45367

AN:

1411720

Hom.:

2723

Cov.:

AF XY:

0.0317

AC XY:

22140

AN XY:

697690

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.0336

Gnomad4 ASJ exome

AF:

0.0354

Gnomad4 EAS exome

AF:

0.000269

Gnomad4 SAS exome

AF:

0.0490

Gnomad4 FIN exome

AF:

0.0230

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0475

GnomAD4 genome

AF:

0.116

AC:

17676

AN:

152118

Hom.:

2655

Cov.:

AF XY:

0.113

AC XY:

8383

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.0567

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0543

Gnomad4 FIN

AF:

0.0194

Gnomad4 NFE

AF:

0.0240

Gnomad4 OTH

AF:

0.0935

Alfa

AF:

0.0411

Hom.:

847

Bravo

AF:

0.128

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0223

AC:

ESP6500AA

AF:

0.326

AC:

1330

ESP6500EA

AF:

0.0242

AC:

202

ExAC

AF:

0.0389

AC:

4607

Asia WGS

AF:

0.0470

AC:

165

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4Other:1

not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 1D

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 02, 2009

- -

Usher syndrome type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.021

T;T;T;.;.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.73

T;T;T;T;T;T;T

MetaRNN

Benign

0.0041

T;T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;.;N;N;.;.;.

MutationTaster

Benign

0.99

P;P;P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.060

N;.;N;.;N;.;.

REVEL

Benign

0.077

Sift

Benign

0.068

T;.;T;.;T;.;.

Sift4G

Benign

0.20

T;T;T;T;T;T;.

Polyphen

0.0

.;.;B;B;.;.;.

Vest4

0.061

ClinPred

0.013

GERP RS

0.54

Varity_R

0.089

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over