17-7260415-G-A

Position:

chr17-7260415-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001307.6(CLDN7):c.595C>T(p.Arg199Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,462 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 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CLDN7
NM_001307.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06544611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN7	NM_001307.6 linkuse as main transcript	c.595C>T	p.Arg199Cys	missense_variant	4/4	ENST00000360325.11	NP_001298.3	O95471-1A0A384ME58
CLDN7	NM_001185022.2 linkuse as main transcript	c.595C>T	p.Arg199Cys	missense_variant	5/5		NP_001171951.1	O95471-1A0A384ME58
CLDN7	NM_001185023.2 linkuse as main transcript	c.*72C>T		3_prime_UTR_variant	3/3		NP_001171952.1	O95471F5H496

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 linkuse as main transcript	c.595C>T	p.Arg199Cys	missense_variant	4/4	1	NM_001307.6	ENSP00000353475.7		O95471-1
ENSG00000262302	ENST00000577138.1 linkuse as main transcript	n.223+1406C>T		intron_variant		3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000252

AC:

AN:

250158

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000181

AC:

265

AN:

1461170

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00246

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000487

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000250

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.595C>T (p.R199C) alteration is located in exon 4 (coding exon 4) of the CLDN7 gene. This alteration results from a C to T substitution at nucleotide position 595, causing the arginine (R) at amino acid position 199 to be replaced by a cysteine (C). 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

0.37

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T

Eigen

Benign

0.023

Eigen_PC

Benign

0.0046

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

.;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.065

T;T

MetaSVM

Uncertain

0.023

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.42

Sift

Benign

0.033

D;D

Sift4G

Benign

0.073

T;T

Polyphen

0.97

D;D

Vest4

0.41

MVP

0.90

MPC

0.82

ClinPred

0.041

GERP RS

3.9

Varity_R

0.14

gMVP

0.57

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