TJP1 p.Val1698Val

Variant names:

• chr15-29704279-T-T
• NM_001330239.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-29704280--
• chr15-29704280-C-A
• chr15-29704280-C-G
• chr15-29704280-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330239.4(TJP1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TJP1 NM_001330239.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• 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]

LCIIAR (HGNC:56346): (lung cancer immune cell infiltration associated lncRNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 27 of 28	NP_001317168.1	A0A087X0K9
	TJP1	NM_001301025.3		c.		exon_region	Exon 28 of 29	NP_001287954.2	G3V1L9
	TJP1	NM_001355012.2		c.		exon_region	Exon 28 of 29	NP_001341941.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP1	ENST00000614355.5	TSL:5 MANE Select	c.		exon_region	Exon 27 of 28	ENSP00000483470.2	A0A087X0K9
	TJP1	ENST00000346128.10	TSL:1	c.		exon_region	Exon 27 of 28	ENSP00000281537.7	Q07157-1
	TJP1	ENST00000400011.6	TSL:1	c.		exon_region	Exon 27 of 28	ENSP00000382890.2	G5E9E7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

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: chr15-29996483;