chr7-73769827-C-A

Variant summary

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

The NM_001306.4(CLDN3):​c.223G>T​(p.Asp75Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D75H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLDN3
NM_001306.4 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86
Variant links:
Genes affected
CLDN3 (HGNC:2045): (claudin 3) Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat. [provided by RefSeq, Jul 2008]

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, 0.882

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN3NM_001306.4 linkc.223G>T p.Asp75Tyr missense_variant Exon 1 of 1 ENST00000395145.3 NP_001297.1 O15551Q75L79

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDN3ENST00000395145.3 linkc.223G>T p.Asp75Tyr missense_variant Exon 1 of 1 6 NM_001306.4 ENSP00000378577.2 O15551

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460160
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726406
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.62
D
Eigen
Uncertain
0.29
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.88
D
MetaSVM
Uncertain
0.38
D
MutationAssessor
Uncertain
2.1
M
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-8.5
D
REVEL
Uncertain
0.63
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.56
Loss of disorder (P = 0.1825);
MVP
0.78
MPC
1.8
ClinPred
1.0
D
GERP RS
4.0
Varity_R
0.92
gMVP
0.97

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: chr7-73184157; API