15-29901265-T-C

Variant names:

• chr15-29901265-T-C
• rs711355
• NM_001301025.3:c.306+54967A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301025.3(TJP1):​c.306+54967A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,048 control chromosomes in the GnomAD database, including 28,911 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 0.61 (28911 hom., cov: 33)
• Consequence: TJP1 NM_001301025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 11 publications found

Genes affected

TJP1 (HGNC:11827): (tight junction protein 1) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, and acts as a tight junction adaptor protein that also regulates adherens junctions. Tight junctions regulate the movement of ions and macromolecules between endothelial and epithelial cells. The multidomain structure of this scaffold protein, including a postsynaptic density 95/disc-large/zona occludens (PDZ) domain, a Src homology (SH3) domain, a guanylate kinase (GuK) domain and unique (U) motifs all help to co-ordinate binding of transmembrane proteins, cytosolic proteins, and F-actin, which are required for tight junction function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

TJP1 Gene-Disease associations (from GenCC):

• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP1	NM_001301025.3	c.306+54967A>G		intron_variant	Intron 2 of 28		NP_001287954.2
TJP1	NM_001355012.2	c.306+54967A>G		intron_variant	Intron 2 of 28		NP_001341941.1
TJP1	XM_017022521.2	c.306+54967A>G		intron_variant	Intron 2 of 29		XP_016878010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP1	ENST00000356107.11	c.306+54967A>G		intron_variant	Intron 2 of 28	5		ENSP00000348416.7
TJP1	ENST00000473741.1	n.63+54967A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92980 AN: 151930 Hom.: 28882 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.612 AC: 93059 AN: 152048 Hom.: 28911 Cov.: 33 AF XY: 0.612 AC XY: 45441 AN XY: 74304

African (AFR) AF: 0.694 AC: 28791 AN: 41492

American (AMR) AF: 0.581 AC: 8873 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2564 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2466 AN: 5158

South Asian (SAS) AF: 0.764 AC: 3676 AN: 4812

European-Finnish (FIN) AF: 0.540 AC: 5702 AN: 10552

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38893 AN: 67966

Other (OTH) AF: 0.634 AC: 1340 AN: 2114

Alfa AF: 0.600 Hom.: 18044

Bravo AF: 0.615

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs711355; hg19: chr15-30193468;