10-71811961-G-C

Variant summary

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

The NM_001171935.1(CDH23):​c.-331G>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDH23
NM_001171935.1 5_prime_UTR_premature_start_codon_gain

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.29
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH23NM_022124.6 linkc.9326G>C p.Arg3109Pro missense_variant Exon 66 of 70 ENST00000224721.12 NP_071407.4 Q9H251-1Q6P152

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH23ENST00000224721.12 linkc.9326G>C p.Arg3109Pro missense_variant Exon 66 of 70 5 NM_022124.6 ENSP00000224721.9 Q9H251-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461190
Hom.:
0
Cov.:
51
AF XY:
0.00000138
AC XY:
1
AN XY:
726876
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.44
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0018
T;T;.;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.69
.;N;.;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.2
.;.;.;N
REVEL
Benign
0.22
Sift
Uncertain
0.0090
.;.;.;D
Sift4G
Uncertain
0.0060
D;.;D;D
Polyphen
0.80
.;P;.;.
Vest4
0.77
MutPred
0.61
Loss of methylation at R3109 (P = 0.0159);Loss of methylation at R3109 (P = 0.0159);.;.;
MVP
0.87
MPC
0.23
ClinPred
0.87
D
GERP RS
5.8
Varity_R
0.40
gMVP
0.61

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: chr10-73571718; API