rs377218278

Variant names:

• chr9-69248202-C-G
• NM_004817.4:c.2858C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-69248202-C-G
• chr9-69248202-C-T

Variant summary

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

The NM_004817.4(TJP2):​c.2858C>G​(p.Ser953Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,454,714 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S953S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TJP2 NM_004817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15

Genes affected

TJP2 (HGNC:11828): (tight junction protein 2) This gene encodes a zonula occluden that is a member of the membrane-associated guanylate kinase homolog family. The encoded protein functions as a component of the tight junction barrier in epithelial and endothelial cells and is necessary for proper assembly of tight junctions. Mutations in this gene have been identified in patients with hypercholanemia, and genomic duplication of a 270 kb region including this gene causes autosomal dominant deafness-51. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ENSG00000285130 (HGNC:):

ACMG classification

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
TJP2	NM_004817.4	c.2858C>G	p.Ser953Trp	missense_variant	Exon 19 of 23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.2858C>G	p.Ser953Trp	missense_variant	Exon 19 of 23	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.3245C>G	p.Ser1082Trp	missense_variant	Exon 21 of 25			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454714 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723168

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.77	.;.;.;D;.;D;.;.;.;.;.;.;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.8	.;.;.;M;M;M;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.8	.;D;.;.;D;D;.;.;.;D;.;D;.
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	.;D;.;.;D;D;.;.;.;D;.;D;.
Sift4G	Pathogenic	0.0	.;D;.;.;D;D;.;.;.;D;.;D;.
Polyphen		1.0	.;.;.;D;D;D;.;.;.;.;.;.;.
Vest4		0.66, 0.56, 0.74, 0.64, 0.74
MutPred		0.24		.;.;.;Loss of phosphorylation at S953 (P = 0.0065);Loss of phosphorylation at S953 (P = 0.0065);Loss of phosphorylation at S953 (P = 0.0065);Loss of phosphorylation at S953 (P = 0.0065);Loss of phosphorylation at S953 (P = 0.0065);.;.;.;.;.;
MVP		0.81
MPC		0.90
ClinPred		1.0	D
GERP RS		6.2
Varity_R		0.76
gMVP		0.59

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: chr9-71863118;