dbSNP rs1046278: TJP3:c.*8A>C (chr19-3750692-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0620

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:

APBA3 (HGNC:580): (amyloid beta precursor protein binding family A member 3) The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. This gene product is believed to be involved in signal transduction processes. This gene is a candidate gene for Alzheimer's disease. [provided by RefSeq, Jul 2008]

APBA3 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TJP3	NM_001267560.2 link	c.*8A>C		3_prime_UTR_variant	Exon 21 of 21	ENST00000541714.7	NP_001254489.1	O95049-1
APBA3	NM_004886.4 link	c.*334T>G		downstream_gene_variant		ENST00000316757.4	NP_004877.1	O96018

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP3	ENST00000541714.7 link	c.*8A>C		3_prime_UTR_variant	Exon 21 of 21	2	NM_001267560.2	ENSP00000439278.1		O95049-1
APBA3	ENST00000316757.4 link	c.*334T>G		downstream_gene_variant		1	NM_004886.4	ENSP00000315136.2		O96018

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82971

AN:

151904

Hom.:

23007

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.555

AC XY:

393797

AN XY:

709914

show subpopulations

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.:

AF XY:

0.550

AC XY:

40851

AN XY:

74274

show subpopulations

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over