chr19-3750617-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001267560.2(TJP3):c.2693T>C(p.Met898Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,605,634 control chromosomes in the GnomAD database, including 243,832 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20484 hom., cov: 31)

Exomes 𝑓: 0.55 ( 223348 hom. )

Consequence

TJP3
NM_001267560.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

32 publications found

Variant links:

Genes affected

TJP3 (HGNC:11829): (tight junction protein 3) The protein encoded by this gene is a member of the membrane-associated guanylate kinase-like (MAGUK) protein family which is characterized by members having multiple PDZ domains, a single SH3 domain, and a single guanylate kinase-like (GUK)-domain. In addition, members of the zonula occludens protein subfamily have an acidic domain, a basic arginine-rich region, and a proline-rich domain. The protein encoded by this gene plays a role in the linkage between the actin cytoskeleton and tight-junctions and also sequesters cyclin D1 at tight junctions during mitosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene has a partial pseudogene on chromosome 1. [provided by RefSeq, May 2012]

TJP3 links:

APBA3 (HGNC:580): (amyloid beta precursor protein binding family A member 3) The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. This gene product is believed to be involved in signal transduction processes. This gene is a candidate gene for Alzheimer's disease. [provided by RefSeq, Jul 2008]

APBA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3942548E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267560.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TJP3	NM_001267560.2	MANE Select	c.2693T>C	p.Met898Thr	missense	Exon 21 of 21	NP_001254489.1
TJP3	NM_001267561.2		c.2720T>C	p.Met907Thr	missense	Exon 21 of 21	NP_001254490.1
APBA3	NM_004886.4	MANE Select	c.*409A>G		downstream_gene	N/A	NP_004877.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TJP3	ENST00000541714.7	TSL:2 MANE Select	c.2693T>C	p.Met898Thr	missense	Exon 21 of 21	ENSP00000439278.1
TJP3	ENST00000587686.1	TSL:1	c.2750T>C	p.Met917Thr	missense	Exon 20 of 20	ENSP00000467864.1
TJP3	ENST00000589378.5	TSL:2	c.2720T>C	p.Met907Thr	missense	Exon 21 of 21	ENSP00000465419.1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

76964

AN:

151580

Hom.:

20461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.645

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.546

GnomAD2 exomes

AF:

0.569

AC:

136125

AN:

239428

AF XY:

0.566

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.542

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.552

AC:

802147

AN:

1453936

Hom.:

223348

Cov.:

AF XY:

0.552

AC XY:

398620

AN XY:

722690

show subpopulations

African (AFR)

AF:

0.334

AC:

11173

AN:

33418

American (AMR)

AF:

0.709

AC:

30924

AN:

43594

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

14465

AN:

25896

East Asian (EAS)

AF:

0.691

AC:

27303

AN:

39536

South Asian (SAS)

AF:

0.561

AC:

47715

AN:

85124

European-Finnish (FIN)

AF:

0.570

AC:

30134

AN:

52866

Middle Eastern (MID)

AF:

0.532

AC:

3066

AN:

5760

European-Non Finnish (NFE)

AF:

0.546

AC:

604415

AN:

1107638

Other (OTH)

AF:

0.548

AC:

32952

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

19808

39617

59425

79234

99042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17114

34228

51342

68456

85570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.508

AC:

77043

AN:

151698

Hom.:

20484

Cov.:

AF XY:

0.512

AC XY:

37976

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.345

AC:

14290

AN:

41432

American (AMR)

AF:

0.646

AC:

9845

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1933

AN:

3464

East Asian (EAS)

AF:

0.653

AC:

3347

AN:

5122

South Asian (SAS)

AF:

0.579

AC:

2789

AN:

4814

European-Finnish (FIN)

AF:

0.582

AC:

6104

AN:

10488

Middle Eastern (MID)

AF:

0.510

AC:

149

AN:

292

European-Non Finnish (NFE)

AF:

0.546

AC:

37068

AN:

67828

Other (OTH)

AF:

0.552

AC:

1161

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1863

3726

5590

7453

9316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

684

1368

2052

2736

3420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.537

Hom.:

98895

Bravo

AF:

0.508

TwinsUK

AF:

0.530

AC:

1965

ALSPAC

AF:

0.537

AC:

2068

ESP6500AA

AF:

0.355

AC:

1563

ESP6500EA

AF:

0.554

AC:

4762

ExAC

AF:

0.548

AC:

66395

Asia WGS

AF:

0.630

AC:

2190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.3

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.065

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

PhyloP100

1.4

PrimateAI

Benign

0.43

PROVEAN

Benign

1.2

REVEL

Benign

0.029

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.063

MPC

0.14

ClinPred

0.0016

GERP RS

2.4

Varity_R

0.038

gMVP

0.075

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over