NM_022124.6:c.8401T>A

Variant names:

• chr10-71807608-T-A
• NM_022124.6:c.8401T>A

Variant summary

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

The NM_022124.6(CDH23):​c.8401T>A​(p.Phe2801Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. F2801V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

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 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=0.14597163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.8401T>A	p.Phe2801Ile	missense_variant	Exon 59 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.1681T>A	p.Phe561Ile	missense_variant	Exon 12 of 23		NP_001165404.1
CDH23	NM_001171934.1	c.1681T>A	p.Phe561Ile	missense_variant	Exon 12 of 22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.8401T>A	p.Phe2801Ile	missense_variant	Exon 59 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0032	T;T;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.38	.;N;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.9	.;.;.;N
REVEL	Benign	0.073
Sift	Benign	0.36	.;.;.;T
Sift4G	Benign	1.0	T;.;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.26
MutPred		0.49		Gain of methylation at K2804 (P = 0.1431);Gain of methylation at K2804 (P = 0.1431);.;.;
MVP		0.60
MPC		0.20
ClinPred		0.73	D
GERP RS		3.1
Varity_R		0.28
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-73567365;