19-3739003-C-T

Position:

• chr19-3739003-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001267560.2(TJP3):​c.1500C>T​(p.Asp500Asp) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950

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]

ACMG classification

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	Protein	UniProt
TJP3	NM_001267560.2	c.1500C>T	p.Asp500Asp	synonymous_variant	13/21	ENST00000541714.7	NP_001254489.1
TJP3	NM_001267561.2	c.1527C>T	p.Asp509Asp	synonymous_variant	13/21		NP_001254490.1
TJP3	XM_047438611.1	c.1698C>T	p.Asp566Asp	synonymous_variant	13/21		XP_047294567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP3	ENST00000541714.7	c.1500C>T	p.Asp500Asp	synonymous_variant	13/21	2	NM_001267560.2	ENSP00000439278.1
TJP3	ENST00000587686.1	c.1557C>T	p.Asp519Asp	synonymous_variant	12/20	1		ENSP00000467864.1
TJP3	ENST00000589378.5	c.1527C>T	p.Asp509Asp	synonymous_variant	13/21	2		ENSP00000465419.1
TJP3	ENST00000539908.6	c.1392C>T	p.Asp464Asp	synonymous_variant	12/20	2		ENSP00000439991.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152238 Hom.: 2 Cov.: 33

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.: 6 AF XY: 0.00180 AC XY: 244 AN XY: 135390

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.: 14 Cov.: 33 AF XY: 0.00310 AC XY: 2254 AN XY: 726672

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.: 2 Cov.: 33 AF XY: 0.00230 AC XY: 171 AN XY: 74504

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.: 1

Bravo AF: 0.00262

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs56138006; hg19: chr19-3739001;