17-7260892-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001307.6(CLDN7):c.317G>T(p.Arg106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CLDN7
NM_001307.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3847314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN7	NM_001307.6 link	c.317G>T	p.Arg106Leu	missense_variant	Exon 2 of 4	ENST00000360325.11	NP_001298.3	O95471-1A0A384ME58
CLDN7	NM_001185022.2 link	c.317G>T	p.Arg106Leu	missense_variant	Exon 3 of 5		NP_001171951.1	O95471-1A0A384ME58
CLDN7	NM_001185023.2 link	c.317G>T	p.Arg106Leu	missense_variant	Exon 2 of 3		NP_001171952.1	O95471F5H496

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 link	c.317G>T	p.Arg106Leu	missense_variant	Exon 2 of 4	1	NM_001307.6	ENSP00000353475.7		O95471-1
ENSG00000262302	ENST00000577138.1 link	n.223+929G>T		intron_variant	Intron 1 of 3	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727240

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317G>T (p.R106L) alteration is located in exon 2 (coding exon 2) of the CLDN7 gene. This alteration results from a G to T substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

D;D;D;.;D;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.92

.;D;D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.38

T;T;T;T;T;T

MetaSVM

Uncertain

-0.099

MutationAssessor

Uncertain

2.5

M;.;M;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.8

D;D;D;.;.;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.025

D;D;D;.;.;.

Sift4G

Benign

0.13

T;D;T;.;.;.

Polyphen

0.058

B;B;B;.;.;.

Vest4

0.20

MutPred

0.62

Loss of MoRF binding (P = 0.0385);Loss of MoRF binding (P = 0.0385);Loss of MoRF binding (P = 0.0385);.;.;Loss of MoRF binding (P = 0.0385);

MVP

0.89

MPC

0.58

ClinPred

0.95

GERP RS

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over