NM_001330239.4:c.4373-88G>A

Variant names:

• chr15-29709124-C-T
• rs17683205
• NM_001330239.4:c.4373-88G>A

Variant summary

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

The NM_001330239.4(TJP1):​c.4373-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,310,008 control chromosomes in the GnomAD database, including 8,799 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 0.10 (869 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7930 hom.)
• Consequence: TJP1 NM_001330239.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

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.4373-88G>A		intron	N/A	NP_001317168.1	A0A087X0K9
	TJP1	NM_001301025.3		c.4652-88G>A		intron	N/A	NP_001287954.2	G3V1L9
	TJP1	NM_001355012.2		c.4652-88G>A		intron	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.4373-88G>A		intron	N/A	ENSP00000483470.2	A0A087X0K9
	TJP1	ENST00000346128.10	TSL:1	c.4373-88G>A		intron	N/A	ENSP00000281537.7	Q07157-1
	TJP1	ENST00000400011.6	TSL:1	c.4145-88G>A		intron	N/A	ENSP00000382890.2	G5E9E7

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15513 AN: 152002 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0674

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.111 AC: 128059 AN: 1157888 Hom.: 7930 AF XY: 0.114 AC XY: 66165 AN XY: 578788

African (AFR) AF: 0.0661 AC: 1710 AN: 25870

American (AMR) AF: 0.156 AC: 4772 AN: 30638

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2138 AN: 19394

East Asian (EAS) AF: 0.0861 AC: 3189 AN: 37020

South Asian (SAS) AF: 0.230 AC: 15205 AN: 66118

European-Finnish (FIN) AF: 0.0985 AC: 4486 AN: 45522

Middle Eastern (MID) AF: 0.146 AC: 645 AN: 4432

European-Non Finnish (NFE) AF: 0.102 AC: 90024 AN: 879420

Other (OTH) AF: 0.119 AC: 5890 AN: 49474

GnomAD4 genome AF: 0.102 AC: 15509 AN: 152120 Hom.: 869 Cov.: 32 AF XY: 0.103 AC XY: 7688 AN XY: 74374

African (AFR) AF: 0.0673 AC: 2793 AN: 41512

American (AMR) AF: 0.150 AC: 2287 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3470

East Asian (EAS) AF: 0.126 AC: 648 AN: 5160

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4816

European-Finnish (FIN) AF: 0.0937 AC: 992 AN: 10588

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6992 AN: 67996

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.100 Hom.: 336

Bravo AF: 0.102

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.097
DANN	Benign	0.63
PhyloP100		-2.6
PromoterAI		0.0027	Neutral
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: rs17683205; hg19: chr15-30001328; COSMIC: COSV62043696; COSMIC: COSV62043696;