chr7-101234302-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014343.3(CLDN15):​c.358G>T​(p.Ala120Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000392 in 1,608,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

CLDN15
NM_014343.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44
Variant links:
Genes affected
CLDN15 (HGNC:2036): (claudin 15) 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. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2010]

Genome browser will be placed here

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 rank MANE Protein UniProt
CLDN15NM_014343.3 linkc.358G>T p.Ala120Ser missense_variant Exon 2 of 5 ENST00000308344.10 NP_055158.1 P56746
CLDN15NM_001185080.2 linkc.358G>T p.Ala120Ser missense_variant Exon 3 of 6 NP_001172009.1 P56746

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN15ENST00000308344.10 linkc.358G>T p.Ala120Ser missense_variant Exon 2 of 5 1 NM_014343.3 ENSP00000308870.5 P56746

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
6
AN:
246180
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000412
AC:
60
AN:
1456526
Hom.:
0
Cov.:
31
AF XY:
0.0000428
AC XY:
31
AN XY:
724908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.358G>T (p.A120S) alteration is located in exon 3 (coding exon 2) of the CLDN15 gene. This alteration results from a G to T substitution at nucleotide position 358, causing the alanine (A) at amino acid position 120 to be replaced by a serine (S). 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
Benign
0.10
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.52
D;D;.
Eigen
Benign
-0.081
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.72
.;T;T
M_CAP
Uncertain
0.099
D
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
1.3
L;L;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.90
N;N;N
REVEL
Uncertain
0.38
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.075
T;T;.
Polyphen
0.63
P;P;.
Vest4
0.47
MVP
0.78
MPC
0.69
ClinPred
0.30
T
GERP RS
4.6
Varity_R
0.073
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs374570698; hg19: chr7-100877583; API