Variant chr6-43500763-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001350562.2(TJAP1):c.119A>G(p.Glu40Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TJAP1
NM_001350562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Variant links:

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 links:

TJAP1 (HGNC:):

TJAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJAP1	NM_001350562.2 linkuse as main transcript	c.119A>G	p.Glu40Gly	missense_variant	5/11	ENST00000372449.6	NP_001337491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJAP1	ENST00000372449.6 linkuse as main transcript	c.119A>G	p.Glu40Gly	missense_variant	5/11	5	NM_001350562.2	ENSP00000361527.1		Q5JTD0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2024

The c.119A>G (p.E40G) alteration is located in exon 5 (coding exon 2) of the TJAP1 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the glutamic acid (E) at amino acid position 40 to be replaced by a glycine (G). 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

0.20

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

.;T;.;.;T;.;.;T;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

.;.;D;D;D;.;.;.;D;D

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.031

MutationAssessor

Benign

1.5

L;L;L;.;.;L;L;L;L;L

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D;D;D;D;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0030

D;D;D;D;T;D;D;D;D;.

Sift4G

Uncertain

0.0090

D;D;D;D;D;D;D;D;D;D

Polyphen

0.93

P;P;P;.;P;P;P;P;P;.

Vest4

0.33

MutPred

0.19

Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);

MVP

0.89

MPC

0.53

ClinPred

0.95

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.087

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over