NM_002843.4:c.977G>A

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.977G>A(p.Arg326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,764 control chromosomes in the GnomAD database, including 25,135 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 0.19 ( 2919 hom., cov: 31)

Exomes 𝑓: 0.17 ( 22216 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.74

Publications

61 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=0.004000932).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_017018085.2 link	c.929G>A	p.Arg310Gln	missense_variant	Exon 6 of 25		XP_016873574.1
PTPRJ	XM_047427374.1 link	c.1319G>A	p.Arg440Gln	missense_variant	Exon 6 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRJ	ENST00000418331.7 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 25	1	NM_002843.4	ENSP00000400010.2	Q12913-1
PTPRJ	ENST00000440289.6 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 9	1		ENSP00000409733.2	Q12913-2
PTPRJ	ENST00000698881.1 link	c.1319G>A	p.Arg440Gln	missense_variant	Exon 6 of 25			ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28559

AN:

151816

Hom.:

2918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.0992

Gnomad MID

AF:

0.240

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.178

AC:

44759

AN:

251382

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.169

AC:

246521

AN:

1461830

Hom.:

22216

Cov.:

AF XY:

0.172

AC XY:

125146

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.251

AC:

8401

AN:

33480

American (AMR)

AF:

0.109

AC:

4877

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6278

AN:

26136

East Asian (EAS)

AF:

0.241

AC:

9553

AN:

39700

South Asian (SAS)

AF:

0.266

AC:

22970

AN:

86258

European-Finnish (FIN)

AF:

0.0995

AC:

5313

AN:

53390

Middle Eastern (MID)

AF:

0.276

AC:

1591

AN:

5768

European-Non Finnish (NFE)

AF:

0.158

AC:

175950

AN:

1111980

Other (OTH)

AF:

0.192

AC:

11588

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

13434

26868

40303

53737

67171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6420

12840

19260

25680

32100

<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:

0.188

AC:

28577

AN:

151934

Hom.:

2919

Cov.:

AF XY:

0.187

AC XY:

13864

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.248

AC:

10256

AN:

41386

American (AMR)

AF:

0.160

AC:

2452

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

827

AN:

3470

East Asian (EAS)

AF:

0.275

AC:

1415

AN:

5144

South Asian (SAS)

AF:

0.246

AC:

1186

AN:

4812

European-Finnish (FIN)

AF:

0.0992

AC:

1048

AN:

10568

Middle Eastern (MID)

AF:

0.241

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.159

AC:

10802

AN:

67976

Other (OTH)

AF:

0.202

AC:

426

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1170

2340

3511

4681

5851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.175

Hom.:

11337

Bravo

AF:

0.194

TwinsUK

AF:

0.155

AC:

576

ALSPAC

AF:

0.149

AC:

576

ESP6500AA

AF:

0.252

AC:

1111

ESP6500EA

AF:

0.161

AC:

1387

ExAC

AF:

0.180

AC:

21919

Asia WGS

AF:

0.253

AC:

880

AN:

3478

EpiCase

AF:

0.181

EpiControl

AF:

0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0030

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.045

T;T;T;.

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.31

T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.32

.;N;.;N

PhyloP100

-4.7

PrimateAI

Benign

0.18

PROVEAN

Benign

0.58

.;N;.;N

REVEL

Benign

0.042

Sift

Benign

0.49

.;T;.;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.041

MPC

0.26

ClinPred

0.0065

GERP RS

-10

Varity_R

0.013

gMVP

0.14

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

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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