chr10-71511149-T-G

Variant names:

• chr10-71511149-T-G
• rs3802720
• NM_022124.6:c.366T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022124.6(CDH23):​c.366T>G​(p.Val122Val) variant causes a synonymous 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. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. V122V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH23 NM_022124.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 30 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]

CDH23-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.73 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.366T>G	p.Val122Val	synonymous	Exon 6 of 70	NP_071407.4
	CDH23	NM_001171930.2		c.366T>G	p.Val122Val	synonymous	Exon 6 of 32	NP_001165401.1	A0A087WYR8
	CDH23	NM_001171931.2		c.366T>G	p.Val122Val	synonymous	Exon 6 of 26	NP_001165402.1	Q8N5B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.366T>G	p.Val122Val	synonymous	Exon 6 of 70	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.366T>G	p.Val122Val	synonymous	Exon 6 of 32	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.366T>G	p.Val122Val	synonymous	Exon 6 of 32	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 54818

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.67
PhyloP100		-1.7
PromoterAI		-0.019	Neutral

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: rs3802720; hg19: chr10-73270906;