rs397517320

chr10-71707035-G-Achr10-71707035-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_022124.6(CDH23):c.3092G>A(p.Ser1031Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,453,118 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1031T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34122655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.3092G>A	p.Ser1031Asn	missense_variant	26/70	ENST00000224721.12
CDH23	NM_001171930.2	c.3092G>A	p.Ser1031Asn	missense_variant	26/32
CDH23	NM_001171931.2	c.3092G>A	p.Ser1031Asn	missense_variant	26/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.3092G>A	p.Ser1031Asn	missense_variant	26/70	5	NM_022124.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000388 AC: 9 AN: 232202 Hom.: 0 AF XY: 0.00000793 AC XY: 1 AN XY: 126156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000274

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000826 AC: 12 AN: 1453118 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 721962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;T;.;T;.
Eigen	Benign	0.032
Eigen_PC	Benign	0.067
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
Sift4G	Uncertain	0.026	D;D;.;D;D;.
Polyphen		0.39	.;.;B;.;.;.
Vest4		0.91
MutPred		0.50		Gain of catalytic residue at S1031 (P = 0.2435);Gain of catalytic residue at S1031 (P = 0.2435);Gain of catalytic residue at S1031 (P = 0.2435);Gain of catalytic residue at S1031 (P = 0.2435);Gain of catalytic residue at S1031 (P = 0.2435);Gain of catalytic residue at S1031 (P = 0.2435);
MVP		0.64
ClinPred		0.47	T
GERP RS		4.4
Varity_R		0.24
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs397517320; hg19: chr10-73466792;