rs140072479

Variant names:

• chr16-66909363-C-A
• NM_004062.4:c.2296G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-66909363-C-A
• chr16-66909363-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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]

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=0.13558456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH16	NM_004062.4	c.2296G>T	p.Val766Leu	missense_variant	Exon 17 of 18	ENST00000299752.9	NP_004053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH16	ENST00000299752.9	c.2296G>T	p.Val766Leu	missense_variant	Exon 17 of 18	1	NM_004062.4	ENSP00000299752.4

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

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;