rs140072479

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004062.4(CDH16):​c.2296G>T​(p.Val766Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,252,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. V766M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

CDH16
NM_004062.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391
Variant links:
Genes affected
CDH16 (HGNC:1755): (cadherin 16) This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. Mapped to a previously identified cluster of cadherin genes on chromosome 16q22.1, the gene localizes with superfamily members CDH1, CDH3, CDH5, CDH8 and CDH11. The protein consists of an extracellular domain containing 6 cadherin domains, a transmembrane region and a truncated cytoplasmic domain but lacks the prosequence and tripeptide HAV adhesion recognition sequence typical of most classical cadherins. Expression is exclusively in kidney, where the protein functions as the principal mediator of homotypic cellular recognition, playing a role in the morphogenic direction of tissue development. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

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ACMG classification

Classification made for transcript

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=0.13558456).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH16NM_004062.4 linkc.2296G>T p.Val766Leu missense_variant Exon 17 of 18 ENST00000299752.9 NP_004053.1 O75309-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH16ENST00000299752.9 linkc.2296G>T p.Val766Leu missense_variant Exon 17 of 18 1 NM_004062.4 ENSP00000299752.4 O75309-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.98e-7
AC:
1
AN:
1252710
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
621766
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:
0.00000102
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
Benign
0.15
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
8.0
DANN
Benign
0.96
DEOGEN2
Benign
0.025
.;T;.;T;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.67
T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.14
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;L;.;.;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.2
N;N;N;N;N
REVEL
Benign
0.071
Sift
Benign
0.051
T;T;T;T;T
Sift4G
Benign
0.32
T;T;T;T;T
Polyphen
0.0
B;B;.;.;.
Vest4
0.26
MutPred
0.59
.;Loss of catalytic residue at V766 (P = 0.0469);.;.;.;
MVP
0.43
MPC
0.067
ClinPred
0.33
T
GERP RS
0.81
Varity_R
0.070
gMVP
0.28

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: chr16-66943266; API