rs1046278

Positions:

• chr19-3750692-A-C
• chr19-3750692-A-G
• chr19-3750692-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001267560.2(TJP3):​c.*8A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,584,462 control chromosomes in the GnomAD database, including 245,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23036 hom., cov: 32)
  • Exomes 𝑓: 0.56 (222181 hom.)
• Consequence: TJP3 NM_001267560.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP3	NM_001267560.2	c.*8A>C		3_prime_UTR_variant	21/21	ENST00000541714.7	NP_001254489.1
TJP3	NM_001267561.2	c.*8A>C		3_prime_UTR_variant	21/21		NP_001254490.1
TJP3	XM_047438611.1	c.*8A>C		3_prime_UTR_variant	21/21		XP_047294567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP3	ENST00000541714.7	c.*8A>C		3_prime_UTR_variant	21/21	2	NM_001267560.2	ENSP00000439278.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82971 AN: 151904 Hom.: 23007 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.574

GnomAD3 exomes AF: 0.579 AC: 119916 AN: 206970 Hom.: 35012 AF XY: 0.575 AC XY: 63954 AN XY: 111292

Gnomad AFR exome AF: 0.475

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.649

Gnomad SAS exome AF: 0.568

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.555 AC: 795358 AN: 1432440 Hom.: 222181 Cov.: 35 AF XY: 0.555 AC XY: 393797 AN XY: 709914

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.690

Gnomad4 SAS exome AF: 0.562

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.546

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.546 AC: 83066 AN: 152022 Hom.: 23036 Cov.: 32 AF XY: 0.550 AC XY: 40851 AN XY: 74274

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.580

Alfa AF: 0.563 Hom.: 32902

Bravo AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.64

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: rs1046278; hg19: chr19-3750690;