Variant chr15-29716773-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001330239.4(TJP1):c.4040A>C(p.Asp1347Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 1,614,036 control chromosomes in the GnomAD database, including 2,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.044 ( 167 hom., cov: 33)

Exomes 𝑓: 0.059 ( 2786 hom. )

Consequence

TJP1
NM_001330239.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.67

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036012828).

BP6

Variant 15-29716773-T-G is Benign according to our data. Variant chr15-29716773-T-G is described in ClinVar as [Benign]. Clinvar id is 3056593.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP1	NM_001330239.4 linkuse as main transcript	c.4040A>C	p.Asp1347Ala	missense_variant	23/28	ENST00000614355.5	NP_001317168.1	A0A087X0K9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP1	ENST00000614355.5 linkuse as main transcript	c.4040A>C	p.Asp1347Ala	missense_variant	23/28	5	NM_001330239.4	ENSP00000483470.2		A0A087X0K9

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6754

AN:

152154

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0218

Gnomad ASJ

AF:

0.0544

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.0777

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0587

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0494

AC:

12333

AN:

249524

Hom.:

403

AF XY:

0.0528

AC XY:

7151

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0518

Gnomad EAS exome

AF:

0.0343

Gnomad SAS exome

AF:

0.0862

Gnomad FIN exome

AF:

0.0499

Gnomad NFE exome

AF:

0.0545

Gnomad OTH exome

AF:

0.0492

GnomAD4 exome

AF:

0.0585

AC:

85583

AN:

1461764

Hom.:

2786

Cov.:

AF XY:

0.0595

AC XY:

43282

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0225

Gnomad4 AMR exome

AF:

0.0205

Gnomad4 ASJ exome

AF:

0.0554

Gnomad4 EAS exome

AF:

0.0277

Gnomad4 SAS exome

AF:

0.0835

Gnomad4 FIN exome

AF:

0.0505

Gnomad4 NFE exome

AF:

0.0609

Gnomad4 OTH exome

AF:

0.0578

GnomAD4 genome

AF:

0.0444

AC:

6756

AN:

152272

Hom.:

167

Cov.:

AF XY:

0.0437

AC XY:

3253

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0239

Gnomad4 AMR

AF:

0.0218

Gnomad4 ASJ

AF:

0.0544

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.0774

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.0588

Gnomad4 OTH

AF:

0.0425

Alfa

AF:

0.0536

Hom.:

585

Bravo

AF:

0.0401

TwinsUK

AF:

0.0626

AC:

232

ALSPAC

AF:

0.0695

AC:

268

ESP6500AA

AF:

0.0273

AC:

102

ESP6500EA

AF:

0.0572

AC:

470

ExAC

AF:

0.0490

AC:

5921

Asia WGS

AF:

0.0550

AC:

195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TJP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;T;.;T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D;D;D

MetaRNN

Benign

0.0036

T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.8

L;.;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

D;N;D;.;N

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Benign

0.088

T;D;T;D;D

Polyphen

1.0

D;D;.;.;D

Vest4

0.75

MPC

0.44

ClinPred

0.021

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over