10-71712706-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022124.6(CDH23):​c.3262G>C​(p.Val1088Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CDH23
NM_022124.6 missense

Scores

1
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.74
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH23NM_022124.6 linkc.3262G>C p.Val1088Leu missense_variant Exon 28 of 70 ENST00000224721.12 NP_071407.4 Q9H251-1Q6P152
C10orf105NM_001164375.3 linkc.*3230C>G 3_prime_UTR_variant Exon 2 of 2 ENST00000441508.4 NP_001157847.1 Q8TEF2
CDH23NM_001171930.2 linkc.3262G>C p.Val1088Leu missense_variant Exon 28 of 32 NP_001165401.1 Q9H251A0A087WYR8Q6P152
C10orf105NM_001168390.2 linkc.*3230C>G 3_prime_UTR_variant Exon 2 of 2 NP_001161862.1 Q8TEF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH23ENST00000224721.12 linkc.3262G>C p.Val1088Leu missense_variant Exon 28 of 70 5 NM_022124.6 ENSP00000224721.9 Q9H251-1
C10orf105ENST00000441508 linkc.*3230C>G 3_prime_UTR_variant Exon 2 of 2 1 NM_001164375.3 ENSP00000403151.2 Q8TEF2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461346
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T;T;T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.89
D;D;D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Pathogenic
0.75
D;D;D;D;D
MetaSVM
Benign
-0.55
T
MutationAssessor
Benign
1.6
.;.;L;.;.
PrimateAI
Uncertain
0.55
T
REVEL
Benign
0.27
Sift4G
Uncertain
0.019
D;T;.;D;.
Polyphen
0.090
.;.;B;.;.
Vest4
0.46
MutPred
0.64
Loss of catalytic residue at V1088 (P = 0.1802);Loss of catalytic residue at V1088 (P = 0.1802);Loss of catalytic residue at V1088 (P = 0.1802);Loss of catalytic residue at V1088 (P = 0.1802);Loss of catalytic residue at V1088 (P = 0.1802);
MVP
0.66
ClinPred
0.94
D
GERP RS
4.0
Varity_R
0.098
gMVP
0.58

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: chr10-73472463; API