16-66908457-T-G

Variant names:

• chr16-66908457-T-G
• NM_004062.4:c.2425A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004062.4(CDH16):​c.2425A>C​(p.Thr809Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH16 NM_004062.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.494
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13420495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004062.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH16	NM_004062.4	MANE Select	c.2425A>C	p.Thr809Pro	missense	Exon 18 of 18	NP_004053.1	O75309-1
	CDH16	NM_001204744.2		c.2359A>C	p.Thr787Pro	missense	Exon 18 of 18	NP_001191673.1	O75309-2
	CDH16	NM_001204745.2		c.2308A>C	p.Thr770Pro	missense	Exon 18 of 18	NP_001191674.1	O75309-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH16	ENST00000299752.9	TSL:1 MANE Select	c.2425A>C	p.Thr809Pro	missense	Exon 18 of 18	ENSP00000299752.4	O75309-1
	CDH16	ENST00000394055.7	TSL:1	c.2359A>C	p.Thr787Pro	missense	Exon 18 of 18	ENSP00000377619.3	O75309-2
	CDH16	ENST00000568632.5	TSL:1	c.2134A>C	p.Thr712Pro	missense	Exon 17 of 17	ENSP00000455263.1	O75309-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.49
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.13	T
Sift4G	Uncertain	0.029	D
Polyphen		0.61	P
Vest4		0.38
MutPred		0.41		Gain of glycosylation at T809 (P = 0.0453)
MVP		0.60
MPC		0.22
ClinPred		0.36	T
GERP RS		0.11
Varity_R		0.20
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr16-66942360;