chr19-3750692-A-C

Variant names:

• chr19-3750692-A-C
• rs1046278
• NM_001267560.2:c.*8A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP3	NM_001267560.2	MANE Select	c.*8A>C		3_prime_UTR	Exon 21 of 21	NP_001254489.1
	TJP3	NM_001267561.2		c.*8A>C		3_prime_UTR	Exon 21 of 21	NP_001254490.1
	APBA3	NM_004886.4	MANE Select	c.*334T>G		downstream_gene	N/A	NP_004877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP3	ENST00000541714.7	TSL:2 MANE Select	c.*8A>C		3_prime_UTR	Exon 21 of 21	ENSP00000439278.1
	TJP3	ENST00000587686.1	TSL:1	c.*8A>C		3_prime_UTR	Exon 20 of 20	ENSP00000467864.1
	TJP3	ENST00000586032.5	TSL:5	n.*381A>C		non_coding_transcript_exon	Exon 5 of 5	ENSP00000465065.1

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

GnomAD2 exomes AF: 0.579 AC: 119916 AN: 206970 AF XY: 0.575

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 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

African (AFR) AF: 0.472 AC: 15582 AN: 33038

American (AMR) AF: 0.715 AC: 28680 AN: 40136

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 14369 AN: 25604

East Asian (EAS) AF: 0.690 AC: 26687 AN: 38670

South Asian (SAS) AF: 0.562 AC: 46381 AN: 82598

European-Finnish (FIN) AF: 0.569 AC: 29134 AN: 51178

Middle Eastern (MID) AF: 0.544 AC: 3123 AN: 5740

European-Non Finnish (NFE) AF: 0.546 AC: 598314 AN: 1096138

Other (OTH) AF: 0.558 AC: 33088 AN: 59338

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

African (AFR) AF: 0.474 AC: 19651 AN: 41470

American (AMR) AF: 0.662 AC: 10110 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3468

East Asian (EAS) AF: 0.657 AC: 3384 AN: 5154

South Asian (SAS) AF: 0.582 AC: 2807 AN: 4826

European-Finnish (FIN) AF: 0.586 AC: 6186 AN: 10564

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37240 AN: 67954

Other (OTH) AF: 0.580 AC: 1224 AN: 2112

Alfa AF: 0.563 Hom.: 39770

Bravo AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1046278; hg19: chr19-3750690;