rs3802720

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-71511149-T-C
• chr10-71511149-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022124.6(CDH23):​c.366T>C​(p.Val122Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,613,518 control chromosomes in the GnomAD database, including 367,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V122V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.73 (42372 hom., cov: 32)
  • Exomes 𝑓: 0.66 (325004 hom.)
• Consequence: CDH23 NM_022124.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-71511149-T-C is Benign according to our data. Variant chr10-71511149-T-C is described in ClinVar as Benign. ClinVar VariationId is 45928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

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>C	p.Val122Val	synonymous	Exon 6 of 70	NP_071407.4
	CDH23	NM_001171930.2		c.366T>C	p.Val122Val	synonymous	Exon 6 of 32	NP_001165401.1	A0A087WYR8
	CDH23	NM_001171931.2		c.366T>C	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>C	p.Val122Val	synonymous	Exon 6 of 70	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.366T>C	p.Val122Val	synonymous	Exon 6 of 32	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.366T>C	p.Val122Val	synonymous	Exon 6 of 32	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111543 AN: 151966 Hom.: 42323 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.700

GnomAD2 exomes AF: 0.661 AC: 164866 AN: 249270 AF XY: 0.660

Gnomad AFR exome AF: 0.940

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.660

GnomAD4 exome AF: 0.664 AC: 969722 AN: 1461434 Hom.: 325004 Cov.: 56 AF XY: 0.662 AC XY: 481285 AN XY: 727026

African (AFR) AF: 0.944 AC: 31596 AN: 33480

American (AMR) AF: 0.469 AC: 20957 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 19015 AN: 26136

East Asian (EAS) AF: 0.758 AC: 30110 AN: 39698

South Asian (SAS) AF: 0.607 AC: 52324 AN: 86252

European-Finnish (FIN) AF: 0.726 AC: 38752 AN: 53382

Middle Eastern (MID) AF: 0.700 AC: 4037 AN: 5768

European-Non Finnish (NFE) AF: 0.658 AC: 731668 AN: 1111624

Other (OTH) AF: 0.683 AC: 41263 AN: 60372

GnomAD4 genome AF: 0.734 AC: 111644 AN: 152084 Hom.: 42372 Cov.: 32 AF XY: 0.734 AC XY: 54512 AN XY: 74308

African (AFR) AF: 0.930 AC: 38609 AN: 41516

American (AMR) AF: 0.578 AC: 8838 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2551 AN: 3472

East Asian (EAS) AF: 0.777 AC: 4010 AN: 5158

South Asian (SAS) AF: 0.597 AC: 2875 AN: 4818

European-Finnish (FIN) AF: 0.747 AC: 7896 AN: 10568

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44759 AN: 67956

Other (OTH) AF: 0.697 AC: 1467 AN: 2104

Alfa AF: 0.679 Hom.: 54818

Bravo AF: 0.727

Asia WGS AF: 0.684 AC: 2379 AN: 3478

EpiCase AF: 0.655

EpiControl AF: 0.654

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Autosomal recessive nonsyndromic hearing loss 12 (2)
-	-	2	Usher syndrome type 1D (2)
-	-	1	Usher syndrome type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.65
PhyloP100		-1.7
PromoterAI		0.017	Neutral
Mutation Taster		=83/17	polymorphism (auto)

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; COSMIC: COSV54944416; COSMIC: COSV54944416;