rs483353051

Positions:

• chr10-71732200-C-A
• chr10-71732200-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022124.6(CDH23):​c.3929C>A​(p.Ala1310Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2603933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.3929C>A	p.Ala1310Asp	missense_variant	32/70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2	c.3929C>A	p.Ala1310Asp	missense_variant	32/32		NP_001165401.1
C10orf105	NM_001168390.2	c.-6+5528G>T		intron_variant			NP_001161862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.3929C>A	p.Ala1310Asp	missense_variant	32/70	5	NM_022124.6	ENSP00000224721	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Usher syndrome type 1D Uncertain:1

Uncertain significance, criteria provided, single submitter

literature only

Molecular Genetics Laboratory; Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	.;.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.71	T
REVEL	Benign	0.25
Sift4G	Uncertain	0.0050	D;D;.;D
Polyphen		0.0010	.;.;B;.
Vest4		0.28
MutPred		0.35		.;Gain of disorder (P = 0.0516);Gain of disorder (P = 0.0516);Gain of disorder (P = 0.0516);
MVP		0.75
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.41
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs483353051; hg19: chr10-73491957;