4-183321897-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001185149.1(CLDN24):c.530T>C(p.Leu177Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000076 in 1,579,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
CLDN24
NM_001185149.1 missense
NM_001185149.1 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 6.73
Publications
0 publications found
Genes affected
CLDN24 (HGNC:37200): (claudin 24) 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 75% identical to the mouse homolog. This gene is upstream of the CLDN22 gene, which overlaps the WWC2 gene on the opposite strand in the genome.[provided by RefSeq, Aug 2010]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000526 AC: 8AN: 152148Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
8
AN:
152148
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000206 AC: 4AN: 194092 AF XY: 0.00000956 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
194092
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1427222Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 706754 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1427222
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
706754
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
3
AN:
32504
American (AMR)
AF:
AC:
1
AN:
39426
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25486
East Asian (EAS)
AF:
AC:
0
AN:
37384
South Asian (SAS)
AF:
AC:
0
AN:
81810
European-Finnish (FIN)
AF:
AC:
0
AN:
51152
Middle Eastern (MID)
AF:
AC:
0
AN:
5730
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1094552
Other (OTH)
AF:
AC:
0
AN:
59178
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000011), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.363
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000526 AC: 8AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324 show subpopulations
GnomAD4 genome
AF:
AC:
8
AN:
152148
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74324
show subpopulations
African (AFR)
AF:
AC:
8
AN:
41440
American (AMR)
AF:
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68026
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.530T>C (p.L177P) alteration is located in exon 1 (coding exon 1) of the CLDN24 gene. This alteration results from a T to C substitution at nucleotide position 530, causing the leucine (L) at amino acid position 177 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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