19-3708638-A-G

Position:

• chr19-3708638-A-G

Variant summary

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

The NM_001267560.2(TJP3):​c.-10+77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,700 control chromosomes in the GnomAD database, including 40,720 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 0.73 (40697 hom., cov: 28)
  • Exomes 𝑓: 0.68 (23 hom.)
• Consequence: TJP3 NM_001267560.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP3	NM_001267560.2	c.-10+77A>G		intron_variant		ENST00000541714.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP3	ENST00000541714.7	c.-10+77A>G		intron_variant		2	NM_001267560.2	P4
TJP3	ENST00000539908.6	c.-61+77A>G		intron_variant		2
TJP3	ENST00000590545.5	c.-10+77A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110529 AN: 151480 Hom.: 40653 Cov.: 28

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.676 AC: 69 AN: 102 Hom.: 23 AF XY: 0.703 AC XY: 52 AN XY: 74

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.730 AC: 110634 AN: 151598 Hom.: 40697 Cov.: 28 AF XY: 0.735 AC XY: 54396 AN XY: 74040

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.727

Alfa AF: 0.707 Hom.: 8499

Bravo AF: 0.738

Asia WGS AF: 0.912 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.75

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: rs611481; hg19: chr19-3708636;