Variant chr19-3739003-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001267560.2(TJP3):c.1500C>T(p.Asp500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,096 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 14 hom. )

Consequence

TJP3
NM_001267560.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.950

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 19-3739003-C-T is Benign according to our data. Variant chr19-3739003-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649008.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.95 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TJP3	NM_001267560.2 linkuse as main transcript	c.1500C>T	p.Asp500=	synonymous_variant	13/21	ENST00000541714.7
TJP3	NM_001267561.2 linkuse as main transcript	c.1527C>T	p.Asp509=	synonymous_variant	13/21
TJP3	XM_047438611.1 linkuse as main transcript	c.1698C>T	p.Asp566=	synonymous_variant	13/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP3	ENST00000541714.7 linkuse as main transcript	c.1500C>T	p.Asp500=	synonymous_variant	13/21	2	NM_001267560.2	P4	O95049-1
TJP3	ENST00000587686.1 linkuse as main transcript	c.1557C>T	p.Asp519=	synonymous_variant	12/20	1		A2	O95049-3
TJP3	ENST00000589378.5 linkuse as main transcript	c.1527C>T	p.Asp509=	synonymous_variant	13/21	2		A2	O95049-4
TJP3	ENST00000539908.6 linkuse as main transcript	c.1392C>T	p.Asp464=	synonymous_variant	12/20	2			O95049-5

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

365

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00187

AC:

468

AN:

250052

Hom.:

AF XY:

0.00180

AC XY:

244

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.000648

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00324

AC:

4732

AN:

1460740

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2254

AN XY:

726672

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.000551

Gnomad4 NFE exome

AF:

0.00392

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00240

AC:

365

AN:

152356

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00262

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00344

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

Jul 01, 2022

TJP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.97

DANN

Benign

0.73

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