chr5-31313439-A-T

Variant names:

• chr5-31313439-A-T
• rs1190792875
• NM_004932.4:c.1375A>T

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.1375A>T​(p.Ile459Leu) 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. 16/22 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: 2.73
• 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=0.18795186).

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.1375A>T	p.Ile459Leu	missense	Exon 8 of 12	NP_004923.1	P55285-1
	CDH6	NM_001362435.2		c.1375A>T	p.Ile459Leu	missense	Exon 8 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.1375A>T	p.Ile459Leu	missense	Exon 8 of 12	ENSP00000265071.2	P55285-1
	CDH6	ENST00000514738.5	TSL:1	c.1210A>T	p.Ile404Leu	missense	Exon 8 of 11	ENSP00000424843.1	D6RF86
	CDH6	ENST00000899823.1		c.1375A>T	p.Ile459Leu	missense	Exon 9 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: 0.0000113

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	0.13
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.090
Sift	Benign	0.93	T
Sift4G	Benign	0.97	T
Polyphen		0.0080	B
Vest4		0.39
MutPred		0.40		Gain of disorder (P = 0.2233)
MVP		0.37
MPC		0.62
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.32
Mutation Taster		=63/37	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: rs1190792875; hg19: chr5-31313546;