8-8702882-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_194284.3(CLDN23):āc.484C>Gā(p.Leu162Val) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,580,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., cov: 33)
Exomes š: 0.000097 ( 0 hom. )
Consequence
CLDN23
NM_194284.3 missense
NM_194284.3 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 3.77
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 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLDN23 | NM_194284.3 | c.484C>G | p.Leu162Val | missense_variant | 1/1 | ENST00000519106.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLDN23 | ENST00000519106.2 | c.484C>G | p.Leu162Val | missense_variant | 1/1 | NM_194284.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000603 AC: 13AN: 215658Hom.: 0 AF XY: 0.0000501 AC XY: 6AN XY: 119854
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GnomAD4 exome AF: 0.0000973 AC: 139AN: 1428058Hom.: 0 Cov.: 33 AF XY: 0.0000949 AC XY: 67AN XY: 706208
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | The c.484C>G (p.L162V) alteration is located in exon 1 (coding exon 1) of the CLDN23 gene. This alteration results from a C to G substitution at nucleotide position 484, causing the leucine (L) at amino acid position 162 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at L162 (P = 0.0203);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at