7-73769403-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001306.4(CLDN3):​c.647G>A​(p.Arg216His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R216L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CLDN3
NM_001306.4 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22556859).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDN3NM_001306.4 linkc.647G>A p.Arg216His 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.647G>A p.Arg216His missense_variant Exon 1 of 1 6 NM_001306.4 ENSP00000378577.2 O15551

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000431
AC:
1
AN:
232062
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
127922
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000559
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000346
AC:
5
AN:
1446180
Hom.:
0
Cov.:
31
AF XY:
0.00000417
AC XY:
3
AN XY:
719840
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:
0.00000450
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
Benign
0.31
BayesDel_addAF
Uncertain
0.081
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.039
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.23
T
MetaSVM
Uncertain
0.16
D
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.40
Sift
Uncertain
0.026
D
Sift4G
Benign
0.16
T
Polyphen
0.97
D
Vest4
0.16
MutPred
0.26
Gain of methylation at K217 (P = 0.124);
MVP
0.66
MPC
1.4
ClinPred
0.65
D
GERP RS
4.6
Varity_R
0.24
gMVP
0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs868906959; hg19: chr7-73183733; COSMIC: COSV67777470; API