17-7260420-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001307.6(CLDN7):​c.590T>A​(p.Val197Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V197A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CLDN7
NM_001307.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13012403).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN7NM_001307.6 linkc.590T>A p.Val197Glu missense_variant Exon 4 of 4 ENST00000360325.11 NP_001298.3 O95471-1A0A384ME58
CLDN7NM_001185022.2 linkc.590T>A p.Val197Glu missense_variant Exon 5 of 5 NP_001171951.1 O95471-1A0A384ME58
CLDN7NM_001185023.2 linkc.*67T>A 3_prime_UTR_variant Exon 3 of 3 NP_001171952.1 O95471F5H496

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN7ENST00000360325.11 linkc.590T>A p.Val197Glu missense_variant Exon 4 of 4 1 NM_001307.6 ENSP00000353475.7 O95471-1
ENSG00000262302ENST00000577138.1 linkn.223+1401T>A intron_variant Intron 1 of 3 3 ENSP00000460571.1 I3L3M4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
53
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
18
DANN
Benign
0.87
DEOGEN2
Benign
0.10
T;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.18
.;T
M_CAP
Benign
0.071
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.46
N;N
REVEL
Benign
0.16
Sift
Benign
0.19
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.0
B;B
Vest4
0.067
MutPred
0.36
Loss of MoRF binding (P = 0.0219);Loss of MoRF binding (P = 0.0219);
MVP
0.72
MPC
0.66
ClinPred
0.064
T
GERP RS
4.9
Varity_R
0.090
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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.

Other links and lift over

dbSNP: rs4562; hg19: chr17-7163739; API