9-69220926-C-G

Position:

• chr9-69220926-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004817.4(TJP2):​c.382C>G​(p.Gln128Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TJP2 NM_004817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087222576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.382C>G	p.Gln128Glu	missense_variant	5/23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.382C>G	p.Gln128Glu	missense_variant	5/23	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.769C>G	p.Gln257Glu	missense_variant	7/25			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460118 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726356

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.00000745 Hom.: 506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.014	.;.;T;T;.;.;T;.;T;.;.;.;.;.;.;.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.89	D;D;.;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.087	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	.;.;.;.;.;.;M;M;M;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.74	.;N;.;N;.;.;.;N;N;.;.;.;N;.;.;N;.;.
REVEL	Benign	0.033
Sift	Uncertain	0.021	.;D;.;D;.;.;.;D;D;.;.;.;D;.;.;D;.;.
Sift4G	Benign	0.24	.;T;T;T;.;.;.;T;T;.;.;.;T;.;.;T;.;.
Polyphen		0.060, 0.038	.;.;.;.;.;.;B;B;B;.;.;.;.;.;.;.;.;.
Vest4		0.22, 0.21, 0.23, 0.24, 0.29
MutPred		0.29		.;.;.;.;.;.;Loss of MoRF binding (P = 0.0599);Loss of MoRF binding (P = 0.0599);Loss of MoRF binding (P = 0.0599);Loss of MoRF binding (P = 0.0599);Loss of MoRF binding (P = 0.0599);.;.;.;.;.;.;.;
MVP		0.50
MPC		0.25
ClinPred		0.11	T
GERP RS		2.9
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.6
Varity_R		0.083
gMVP		0.33

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

Other links and lift over

dbSNP: rs41305539; hg19: chr9-71835842;