NM_001185149.1:c.431C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_001185149.1(CLDN24):c.431C>T(p.Thr144Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,612,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
CLDN24
NM_001185149.1 missense
NM_001185149.1 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 2.44
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37534368).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000460 AC: 7AN: 152140Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
7
AN:
152140
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: 0.0000410 AC: 10AN: 243698 AF XY: 0.0000377 show subpopulations
GnomAD2 exomes
AF:
AC:
10
AN:
243698
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: 0.0000541 AC: 79AN: 1460304Hom.: 0 Cov.: 34 AF XY: 0.0000633 AC XY: 46AN XY: 726334 show subpopulations
GnomAD4 exome
AF:
AC:
79
AN:
1460304
Hom.:
Cov.:
34
AF XY:
AC XY:
46
AN XY:
726334
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33380
American (AMR)
AF:
AC:
2
AN:
44596
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26076
East Asian (EAS)
AF:
AC:
2
AN:
39618
South Asian (SAS)
AF:
AC:
0
AN:
85958
European-Finnish (FIN)
AF:
AC:
0
AN:
53376
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
67
AN:
1111224
Other (OTH)
AF:
AC:
7
AN:
60316
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
6
12
19
25
31
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000525 AC: 8AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74450 show subpopulations
GnomAD4 genome
AF:
AC:
8
AN:
152258
Hom.:
Cov.:
32
AF XY:
AC XY:
5
AN XY:
74450
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41554
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
2
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
5
AN:
68030
Other (OTH)
AF:
AC:
0
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
5
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Oct 01, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.431C>T (p.T144M) alteration is located in exon 1 (coding exon 1) of the CLDN24 gene. This alteration results from a C to T substitution at nucleotide position 431, causing the threonine (T) at amino acid position 144 to be replaced by a methionine (M). 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
Uncertain
T
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of catalytic residue at V140 (P = 0.0393);
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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