Variant 19-3728675-T-C 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.120T>C(p.Ser40Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,808 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 5 hom. )

Consequence

TJP3
NM_001267560.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.96

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:

TJP3 (HGNC:):

TJP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-3728675-T-C is Benign according to our data. Variant chr19-3728675-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649006.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-7.96 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP3	NM_001267560.2 linkuse as main transcript	c.120T>C	p.Ser40Ser	synonymous_variant	3/21	ENST00000541714.7	NP_001254489.1	O95049-1
TJP3	NM_001267561.2 linkuse as main transcript	c.147T>C	p.Ser49Ser	synonymous_variant	3/21		NP_001254490.1	O95049-4
TJP3	XM_047438611.1 linkuse as main transcript	c.318T>C	p.Ser106Ser	synonymous_variant	3/21		XP_047294567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP3	ENST00000541714.7 linkuse as main transcript	c.120T>C	p.Ser40Ser	synonymous_variant	3/21	2	NM_001267560.2	ENSP00000439278.1		O95049-1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

232

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00144

AC:

359

AN:

248886

Hom.:

AF XY:

0.00151

AC XY:

203

AN XY:

134484

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00192

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.00344

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00117

AC:

1711

AN:

1461520

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

854

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000523

Gnomad4 FIN exome

AF:

0.00350

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00152

AC:

232

AN:

152288

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00117

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00142

EpiControl

AF:

0.000652

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

Jun 01, 2022

TJP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.084

DANN

Benign

0.49

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.

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