10-71724083-T-C

Variant names:

• chr10-71724083-T-C
• rs1223980355
• NM_022124.6:c.3408T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022124.6(CDH23):​c.3408T>C​(p.Arg1136Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000355 in 1,407,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R1136R) has been classified as Likely benign. The gene CDH23 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CDH23 NM_022124.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 1 publications found

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

Specifications for CDH23 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.059).
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.3408T>C	p.Arg1136Arg	synonymous	Exon 29 of 70	NP_071407.4
	CDH23	NM_001171930.2		c.3408T>C	p.Arg1136Arg	synonymous	Exon 29 of 32	NP_001165401.1	A0A087WYR8
	C10orf105	NM_001168390.2		c.-5-7741A>G		intron	N/A	NP_001161862.1	Q8TEF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.3408T>C	p.Arg1136Arg	synonymous	Exon 29 of 70	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.3408T>C	p.Arg1136Arg	synonymous	Exon 29 of 32	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.3405T>C	p.Arg1135Arg	synonymous	Exon 29 of 32	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000602 AC: 1 AN: 166218 AF XY: 0.00

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: 0.0000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000355 AC: 5 AN: 1407530 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 695006

African (AFR) AF: 0.00 AC: 0 AN: 32072

American (AMR) AF: 0.00 AC: 0 AN: 36638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25234

East Asian (EAS) AF: 0.00 AC: 0 AN: 36540

South Asian (SAS) AF: 0.00 AC: 0 AN: 79584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000461 AC: 5 AN: 1083568

Other (OTH) AF: 0.00 AC: 0 AN: 58372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.31
DANN	Benign	0.56
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs1223980355; hg19: chr10-73483840;