rs763380903

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_194284.3(CLDN23):​c.301G>A​(p.Gly101Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G101C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

CLDN23
NM_194284.3 missense

Scores

12
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.35
Variant links:
Genes affected
CLDN23 (HGNC:17591): (claudin 23) 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. This gene is expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN23NM_194284.3 linkc.301G>A p.Gly101Ser missense_variant Exon 1 of 1 ENST00000519106.2 NP_919260.2 Q96B33

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN23ENST00000519106.2 linkc.301G>A p.Gly101Ser missense_variant Exon 1 of 1 6 NM_194284.3 ENSP00000428780.1 Q96B33

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Pathogenic
0.49
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.68
D
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Pathogenic
0.75
D
MetaRNN
Pathogenic
0.94
D
MetaSVM
Pathogenic
0.81
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-5.4
D
REVEL
Pathogenic
0.90
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.94
P
Vest4
0.86
MutPred
0.72
Loss of catalytic residue at V102 (P = 0.1266);
MVP
0.91
MPC
0.75
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.72
gMVP
0.88

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: rs763380903; hg19: chr8-8560209; API