Variant 19-3730627-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001267560.2(TJP3):c.534C>T(p.Ser178Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000354 in 1,611,852 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

TJP3
NM_001267560.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.20

Variant links:

Genes affected

TJP3 (HGNC:11829): (tight junction protein 3) The protein encoded by this gene is a member of the membrane-associated guanylate kinase-like (MAGUK) protein family which is characterized by members having multiple PDZ domains, a single SH3 domain, and a single guanylate kinase-like (GUK)-domain. In addition, members of the zonula occludens protein subfamily have an acidic domain, a basic arginine-rich region, and a proline-rich domain. The protein encoded by this gene plays a role in the linkage between the actin cytoskeleton and tight-junctions and also sequesters cyclin D1 at tight junctions during mitosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene has a partial pseudogene on chromosome 1. [provided by RefSeq, May 2012]

TJP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-3730627-C-T is Benign according to our data. Variant chr19-3730627-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649007.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.2 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP3	NM_001267560.2 link	c.534C>T	p.Ser178Ser	synonymous_variant	5/21	ENST00000541714.7	NP_001254489.1	O95049-1
TJP3	NM_001267561.2 link	c.561C>T	p.Ser187Ser	synonymous_variant	5/21		NP_001254490.1	O95049-4
TJP3	XM_047438611.1 link	c.732C>T	p.Ser244Ser	synonymous_variant	5/21		XP_047294567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TJP3	ENST00000541714.7 link	c.534C>T	p.Ser178Ser	synonymous_variant	5/21	2	NM_001267560.2	ENSP00000439278.1	O95049-1
TJP3	ENST00000587686.1 link	c.591C>T	p.Ser197Ser	synonymous_variant	4/20	1		ENSP00000467864.1	O95049-3
TJP3	ENST00000589378.5 link	c.561C>T	p.Ser187Ser	synonymous_variant	5/21	2		ENSP00000465419.1	O95049-4
TJP3	ENST00000539908.6 link	c.426C>T	p.Ser142Ser	synonymous_variant	4/20	2		ENSP00000439991.1	O95049-5

Frequencies

GnomAD3 genomes

AF:

0.00166

AC:

252

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00562

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

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:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000467

AC:

114

AN:

243860

Hom.:

AF XY:

0.000330

AC XY:

AN XY:

133238

show subpopulations

Gnomad AFR exome

AF:

0.00600

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000920

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000215

AC:

314

AN:

1459540

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726216

show subpopulations

Gnomad4 AFR exome

AF:

0.00681

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000390

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.00168

AC:

256

AN:

152312

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000743

Hom.:

Bravo

AF:

0.00199

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

TJP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.24

DANN

Benign

0.80

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over