Genetic Variant CLDN7:p.Asn3Ile (chr17-7262036-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001307.6(CLDN7):c.8A>T(p.Asn3Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,714 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CLDN7
NM_001307.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

CLDN7 (HGNC:2049): (claudin 7) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

CLDN7 links:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN7	NM_001307.6 link	c.8A>T	p.Asn3Ile	missense_variant	Exon 1 of 4	ENST00000360325.11	NP_001298.3	O95471-1A0A384ME58
CLDN7	NM_001185022.2 link	c.8A>T	p.Asn3Ile	missense_variant	Exon 2 of 5		NP_001171951.1	O95471-1A0A384ME58
CLDN7	NM_001185023.2 link	c.8A>T	p.Asn3Ile	missense_variant	Exon 1 of 3		NP_001171952.1	O95471F5H496

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 link	c.8A>T	p.Asn3Ile	missense_variant	Exon 1 of 4	1	NM_001307.6	ENSP00000353475.7		O95471-1
ENSG00000262302	ENST00000577138.1 link	n.8A>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245940

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726316

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151474

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000195

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;T;T;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

.;D;D;D;D;D

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.55

D;D;D;D;D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.5

M;.;M;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.0

D;D;D;.;.;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.0030

D;D;D;.;.;.

Sift4G

Uncertain

0.0040

D;D;D;.;D;.

Polyphen

0.94

P;D;P;.;.;.

Vest4

0.36

MutPred

0.32

Loss of disorder (P = 0.0359);Loss of disorder (P = 0.0359);Loss of disorder (P = 0.0359);.;Loss of disorder (P = 0.0359);Loss of disorder (P = 0.0359);

MVP

0.99

MPC

1.1

ClinPred

0.98

GERP RS

5.0

Varity_R

0.62

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over