chr6-43504999-A-T

Position:

• chr6-43504999-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001350562.2(TJAP1):​c.818A>T​(p.Asp273Val) variant causes a missense 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. 13/20 in silico tools predict a benign 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: 1.91

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15857115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJAP1	NM_001350562.2	c.818A>T	p.Asp273Val	missense_variant	11/11	ENST00000372449.6	NP_001337491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJAP1	ENST00000372449.6	c.818A>T	p.Asp273Val	missense_variant	11/11	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

Jan 30, 2024

The c.818A>T (p.D273V) alteration is located in exon 11 (coding exon 8) of the TJAP1 gene. This alteration results from a A to T substitution at nucleotide position 818, causing the aspartic acid (D) at amino acid position 273 to be replaced by a valine (V). 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	Benign	0.11
BayesDel_addAF	Benign	0.0066	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	.;T;.;.;.;T;T
Eigen	Benign	0.059
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	.;.;D;.;.;.;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.;.;.;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D;D;D;D;D;D
Sift4G	Benign	0.14	T;T;T;T;T;T;T
Polyphen		0.95	P;D;P;P;P;D;D
Vest4		0.17
MutPred		0.16		.;Gain of glycosylation at P278 (P = 0.1094);.;.;.;Gain of glycosylation at P278 (P = 0.1094);Gain of glycosylation at P278 (P = 0.1094);
MVP		0.31
MPC		0.77
ClinPred		0.82	D
GERP RS		5.1
Varity_R		0.070
gMVP		0.29

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: chr6-43472737;