8-8702670-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_194284.3(CLDN23):​c.272C>A​(p.Thr91Lys) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CLDN23
NM_194284.3 missense

Scores

3
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71
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]

Genome browser will be placed here

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;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN23NM_194284.3 linkc.272C>A p.Thr91Lys 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.272C>A p.Thr91Lys 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

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

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.272C>A (p.T91K) alteration is located in exon 1 (coding exon 1) of the CLDN23 gene. This alteration results from a C to A substitution at nucleotide position 272, causing the threonine (T) at amino acid position 91 to be replaced by a lysine (K). 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
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.48
N
M_CAP
Pathogenic
0.77
D
MetaRNN
Pathogenic
0.84
D
MetaSVM
Uncertain
0.056
D
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.56
Sift
Uncertain
0.015
D
Sift4G
Benign
0.073
T
Polyphen
0.99
D
Vest4
0.53
MutPred
0.58
Gain of ubiquitination at T91 (P = 0.0155);
MVP
0.94
MPC
0.77
ClinPred
0.85
D
GERP RS
3.9
Varity_R
0.24
gMVP
0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-8560180; API