15-29716772-GT-AG

Variant names:

• chr15-29716772-GT-AG
• NM_001330239.4:c.4040_4041delACinsCT
• TJP1 p.Asp1347Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001330239.4(TJP1):​c.4040_4041delACinsCT​(p.Asp1347Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TJP1 NM_001330239.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330239.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP1	NM_001330239.4	MANE Select	c.4040_4041delACinsCT	p.Asp1347Ala	missense	N/A	NP_001317168.1	A0A087X0K9
	TJP1	NM_001301025.3		c.4319_4320delACinsCT	p.Asp1440Ala	missense	N/A	NP_001287954.2	G3V1L9
	TJP1	NM_001355012.2		c.4319_4320delACinsCT	p.Asp1440Ala	missense	N/A	NP_001341941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP1	ENST00000614355.5	TSL:5 MANE Select	c.4040_4041delACinsCT	p.Asp1347Ala	missense	N/A	ENSP00000483470.2	A0A087X0K9
	TJP1	ENST00000346128.10	TSL:1	c.4040_4041delACinsCT	p.Asp1347Ala	missense	N/A	ENSP00000281537.7	Q07157-1
	TJP1	ENST00000400011.6	TSL:1	c.3812_3813delACinsCT	p.Asp1271Ala	missense	N/A	ENSP00000382890.2	G5E9E7

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-30008976;