6-43502339-T-G

Position:

• chr6-43502339-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001350562.2(TJAP1):​c.347T>G​(p.Leu116Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TJAP1 NM_001350562.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.67

Genes affected

TJAP1 (HGNC:17949): (tight junction associated protein 1) This gene encodes a tight junction-associated protein. Incorporation of the encoded protein into tight junctions occurs at a late stage of formation of the junctions. The encoded protein localizes to the Golgi and may function in vesicle trafficking. Alternatively spliced transcript variants have been described. A related pseudogene exists on the X chromosome. [provided by RefSeq, Mar 2009]

TJAP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJAP1	NM_001350562.2	c.347T>G	p.Leu116Arg	missense_variant	7/11	ENST00000372449.6	NP_001337491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJAP1	ENST00000372449.6	c.347T>G	p.Leu116Arg	missense_variant	7/11	5	NM_001350562.2	ENSP00000361527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.347T>G (p.L116R) alteration is located in exon 7 (coding exon 4) of the TJAP1 gene. This alteration results from a T to G substitution at nucleotide position 347, causing the leucine (L) at amino acid position 116 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;.;T;.;.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	.;.;D;D;.;.;.;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.7	L;L;L;.;L;L;L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.5	D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.020	D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;D;D;D
Vest4		0.98
MutPred		0.41		Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);Loss of stability (P = 0.0231);
MVP		0.92
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.87
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-43470077;