Variant 17-7260487-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_001185023.2(CLDN7):c.438G>C(p.Ter146Tyrext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,988 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: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CLDN7
NM_001185023.2 stop_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.411

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Stoplost variant in NM_001185023.2 Downstream stopcodon found after 44 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDN7	NM_001307.6 link	c.523G>C	p.Val175Leu	missense_variant	Exon 4 of 4	ENST00000360325.11	NP_001298.3	O95471-1A0A384ME58
CLDN7	NM_001185023.2 link	c.438G>C	p.Ter146Tyrext*?	stop_lost	Exon 3 of 3		NP_001171952.1	O95471F5H496
CLDN7	NM_001185022.2 link	c.523G>C	p.Val175Leu	missense_variant	Exon 5 of 5		NP_001171951.1	O95471-1A0A384ME58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDN7	ENST00000360325.11 link	c.523G>C	p.Val175Leu	missense_variant	Exon 4 of 4	1	NM_001307.6	ENSP00000353475.7		O95471-1
ENSG00000262302	ENST00000577138.1 link	n.223+1334G>C		intron_variant	Intron 1 of 3	3		ENSP00000460571.1		I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248114

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134424

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:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726806

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.523G>C (p.V175L) alteration is located in exon 4 (coding exon 4) of the CLDN7 gene. This alteration results from a G to C substitution at nucleotide position 523, causing the valine (V) at amino acid position 175 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

0.34

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

4.8

DANN

Benign

0.82

DEOGEN2

Benign

0.34

T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.83

.;T;T

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.33

PROVEAN

Benign

0.60

N;N;.

REVEL

Benign

0.21

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.71

T;T;.

Polyphen

0.0070

B;B;.

Vest4

0.055

MutPred

0.71

Loss of catalytic residue at V175 (P = 0.0328);Loss of catalytic residue at V175 (P = 0.0328);.;

MVP

0.86

MPC

0.39

ClinPred

0.033

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.046

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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