chr3-170432733-C-T

Variant summary

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

The NM_005602.6(CLDN11):​c.601C>T​(p.His201Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CLDN11
NM_005602.6 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22
Variant links:
Genes affected
CLDN11 (HGNC:8514): (claudin 11) 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. The protein encoded by this gene is a major component of central nervous system (CNS) myelin and plays an important role in regulating proliferation and migration of oligodendrocytes. Mouse studies showed that the gene deficiency results in deafness and loss of the Sertoli cell epithelial phenotype in the testis. This protein is a tight junction protein at the human blood-testis barrier (BTB), and the BTB disruption is related to a dysfunction of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Aug 2010]

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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
CLDN11NM_005602.6 linkc.601C>T p.His201Tyr missense_variant Exon 3 of 3 ENST00000064724.8 NP_005593.2 O75508
CLDN11NM_001185056.2 linkc.349C>T p.His117Tyr missense_variant Exon 3 of 3 NP_001171985.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN11ENST00000064724.8 linkc.601C>T p.His201Tyr missense_variant Exon 3 of 3 1 NM_005602.6 ENSP00000064724.4 O75508
ENSG00000285218ENST00000486975.1 linkc.391+9406C>T intron_variant Intron 2 of 3 2 ENSP00000417434.1 B4DFI2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Feb 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

CLDN11: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.62
D
MetaSVM
Uncertain
0.088
D
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.14
N
REVEL
Uncertain
0.47
Sift
Benign
0.040
D
Sift4G
Uncertain
0.048
D
Polyphen
1.0
D
Vest4
0.62
MutPred
0.21
Loss of helix (P = 0.0304);
MVP
0.93
MPC
1.6
ClinPred
0.76
D
GERP RS
5.8
Varity_R
0.13
gMVP
0.83

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.

Other links and lift over

dbSNP: rs1292009249; hg19: chr3-170150521; API