10-71712775-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022124.6(CDH23):c.3331G>T(p.Val1111Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1111I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDH23
NM_022124.6 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0170

Publications

2 publications found

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:

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C10orf105 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.3331G>T	p.Val1111Phe	missense_variant	Exon 28 of 70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152
C10orf105	NM_001164375.3 link	c.*3161C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000441508.4	NP_001157847.1	Q8TEF2
CDH23	NM_001171930.2 link	c.3331G>T	p.Val1111Phe	missense_variant	Exon 28 of 32		NP_001165401.1	Q9H251A0A087WYR8Q6P152
C10orf105	NM_001168390.2 link	c.*3161C>A		3_prime_UTR_variant	Exon 2 of 2		NP_001161862.1	Q8TEF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.3331G>T	p.Val1111Phe	missense_variant	Exon 28 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1
C10orf105	ENST00000441508.4 link	c.*3161C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001164375.3	ENSP00000403151.2		Q8TEF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245702

AF XY:

0.00000748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460678

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53024

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111620

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Vitreoretinopathy

Uncertain:1

Apr 01, 2018

Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.26

CADD

Benign

1.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;D;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Uncertain

0.089

MetaRNN

Uncertain

0.57

D;D;D;D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.1

.;.;M;.;.

PhyloP100

0.017

PrimateAI

Benign

0.29

REVEL

Benign

0.26

Sift4G

Uncertain

0.0030

D;D;.;D;.

Polyphen

0.93

.;.;P;.;.

Vest4

0.61

MutPred

0.58

Loss of phosphorylation at Y1107 (P = 0.2171);Loss of phosphorylation at Y1107 (P = 0.2171);Loss of phosphorylation at Y1107 (P = 0.2171);Loss of phosphorylation at Y1107 (P = 0.2171);Loss of phosphorylation at Y1107 (P = 0.2171);

MVP

0.70

ClinPred

0.76

GERP RS

0.94

Varity_R

0.094

gMVP

0.85

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over