NM_001301025.3:c.307-58884C>G

Variant names:

• chr15-29859586-G-C
• rs1719013
• NM_001301025.3:c.307-58884C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001301025.3(TJP1):​c.307-58884C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TJP1 NM_001301025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 3 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

ENSG00000295789 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301025.3. 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
	TJP1	NM_001301025.3		c.307-58884C>G		intron	N/A	NP_001287954.2
	TJP1	NM_001355012.2		c.307-58884C>G		intron	N/A	NP_001341941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP1	ENST00000356107.11	TSL:5	c.307-58884C>G		intron	N/A	ENSP00000348416.7
	TJP1	ENST00000473741.1	TSL:2	n.64-58884C>G		intron	N/A
	ENSG00000295789	ENST00000732735.1		n.128+13141C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.63
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs1719013; hg19: chr15-30151789;