11-48144715-G-C

Variant names:

Variant summary

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

The NM_002843.4(PTPRJ):c.2616G>C(p.Glu872Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,613,142 control chromosomes in the GnomAD database, including 244,274 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 0.44 ( 18045 hom., cov: 32)

Exomes 𝑓: 0.55 ( 226229 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.98

Publications

44 publications found

Variant links:

Genes affected

PTPRJ (HGNC:9673): (protein tyrosine phosphatase receptor type J) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTPRJ Gene-Disease associations (from GenCC):

hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
thrombocytopenia 10
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
colorectal cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PTPRJ 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=1.0584347E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.2616G>C	p.Glu872Asp	missense_variant	Exon 13 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	XM_017018085.2 link	c.2568G>C	p.Glu856Asp	missense_variant	Exon 13 of 25		XP_016873574.1
PTPRJ	XM_047427374.1 link	c.2958G>C	p.Glu986Asp	missense_variant	Exon 13 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 link	c.2616G>C	p.Glu872Asp	missense_variant	Exon 13 of 25	1	NM_002843.4	ENSP00000400010.2		Q12913-1
PTPRJ	ENST00000698881.1 link	c.2958G>C	p.Glu986Asp	missense_variant	Exon 13 of 25			ENSP00000514003.1		A0A8V8TP51

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67510

AN:

151934

Hom.:

18035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.525

AC:

131735

AN:

250806

AF XY:

0.523

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.549

AC:

802106

AN:

1461090

Hom.:

226229

Cov.:

AF XY:

0.546

AC XY:

396997

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.118

AC:

3938

AN:

33476

American (AMR)

AF:

0.638

AC:

28553

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

14452

AN:

26134

East Asian (EAS)

AF:

0.460

AC:

18252

AN:

39690

South Asian (SAS)

AF:

0.407

AC:

35065

AN:

86248

European-Finnish (FIN)

AF:

0.606

AC:

32350

AN:

53412

Middle Eastern (MID)

AF:

0.504

AC:

2908

AN:

5768

European-Non Finnish (NFE)

AF:

0.572

AC:

635397

AN:

1111268

Other (OTH)

AF:

0.517

AC:

31191

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

18714

37428

56141

74855

93569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.444

AC:

67531

AN:

152052

Hom.:

18045

Cov.:

AF XY:

0.446

AC XY:

33156

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.135

AC:

5617

AN:

41480

American (AMR)

AF:

0.562

AC:

8597

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1912

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2146

AN:

5160

South Asian (SAS)

AF:

0.419

AC:

2013

AN:

4810

European-Finnish (FIN)

AF:

0.608

AC:

6422

AN:

10562

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

39004

AN:

67972

Other (OTH)

AF:

0.472

AC:

996

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1646

3292

4938

6584

8230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.514

Hom.:

6016

Bravo

AF:

0.432

TwinsUK

AF:

0.567

AC:

2101

ALSPAC

AF:

0.578

AC:

2229

ESP6500AA

AF:

0.149

AC:

654

ESP6500EA

AF:

0.576

AC:

4952

ExAC

AF:

0.515

AC:

62488

EpiCase

AF:

0.567

EpiControl

AF:

0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0090

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.051

T;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

T;T;T

MetaRNN

Benign

0.0000011

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

.;N;.

PhyloP100

-4.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.31

.;N;.

REVEL

Benign

0.019

Sift

Benign

0.65

.;T;.

Sift4G

Benign

0.53

T;T;T

Polyphen

0.0070

.;B;.

Vest4

0.032

MutPred

0.21

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MPC

0.21

ClinPred

0.020

GERP RS

-11

Varity_R

0.031

gMVP

0.23

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-48144715-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over