5-31316243-A-G

Variant names:

• chr5-31316243-A-G
• rs995046641
• NM_004932.4:c.1426A>G

Variant summary

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

The NM_004932.4(CDH6):​c.1426A>G​(p.Ile476Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: CDH6 NM_004932.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10
• Publications: 0 publications found

Genes affected

CDH6 (HGNC:1765): (cadherin 6) This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 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=0.26377067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004932.4. 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
	CDH6	NM_004932.4	MANE Select	c.1426A>G	p.Ile476Val	missense	Exon 9 of 12	NP_004923.1	P55285-1
	CDH6	NM_001362435.2		c.1426A>G	p.Ile476Val	missense	Exon 9 of 11	NP_001349364.1	P55285-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH6	ENST00000265071.3	TSL:2 MANE Select	c.1426A>G	p.Ile476Val	missense	Exon 9 of 12	ENSP00000265071.2	P55285-1
	CDH6	ENST00000514738.5	TSL:1	c.1261A>G	p.Ile421Val	missense	Exon 9 of 11	ENSP00000424843.1	D6RF86
	CDH6	ENST00000899823.1		c.1426A>G	p.Ile476Val	missense	Exon 10 of 13	ENSP00000569882.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.0020
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N
PhyloP100		5.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.084
Sift	Benign	0.26	T
Sift4G	Benign	0.35	T
Polyphen		0.023	B
Vest4		0.41
MutPred		0.48		Loss of ubiquitination at K477 (P = 0.1278)
MVP		0.43
MPC		0.44
ClinPred		0.74	D
GERP RS		3.9
Varity_R		0.046
gMVP		0.33
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs995046641; hg19: chr5-31316350;