rs61739179

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002843.4(PTPRJ):c.1253G>A(p.Arg418His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,614,106 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R418C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 59 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.24

Publications

8 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035292208).

BP6

Variant 11-48127939-G-A is Benign according to our data. Variant chr11-48127939-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 211973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AD,Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PTPRJ	NM_002843.4 link	c.1253G>A	p.Arg418His	missense_variant	Exon 7 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2 link	c.1253G>A	p.Arg418His	missense_variant	Exon 7 of 9		NP_001091973.1
PTPRJ	XM_017018085.2 link	c.1205G>A	p.Arg402His	missense_variant	Exon 7 of 25		XP_016873574.1
PTPRJ	XM_047427374.1 link	c.1595G>A	p.Arg532His	missense_variant	Exon 7 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PTPRJ	ENST00000418331.7 link	c.1253G>A	p.Arg418His	missense_variant	Exon 7 of 25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000440289.6 link	c.1253G>A	p.Arg418His	missense_variant	Exon 7 of 9	1		ENSP00000409733.2
PTPRJ	ENST00000698881.1 link	c.1595G>A	p.Arg532His	missense_variant	Exon 7 of 25			ENSP00000514003.1

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00788

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00593

AC:

1491

AN:

251392

AF XY:

0.00586

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.00667

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00581

AC:

8493

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00582

AC XY:

4234

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33480

American (AMR)

AF:

0.000805

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000765

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0265

AC:

1414

AN:

53412

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00597

AC:

6640

AN:

1112008

Other (OTH)

AF:

0.00505

AC:

305

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

514

1028

1541

2055

2569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

206

412

618

824

1030

<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:

0.00587

AC:

894

AN:

152226

Hom.:

Cov.:

AF XY:

0.00641

AC XY:

477

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41546

American (AMR)

AF:

0.00196

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5170

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0272

AC:

288

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00788

AC:

536

AN:

68008

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

130

174

217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00579

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00617

AC:

ExAC

AF:

0.00564

AC:

685

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00627

EpiControl

AF:

0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PTPRJ: BP4, BS2 -

not specified

Benign:1

Aug 02, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0020

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.059

T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.30

T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

.;N;.;N

PhyloP100

-3.2

PrimateAI

Benign

0.19

PROVEAN

Benign

0.24

.;N;.;N

REVEL

Benign

0.054

Sift

Benign

0.43

.;T;.;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.0070

.;B;.;.

Vest4

0.057

MVP

0.23

MPC

0.29

ClinPred

0.0037

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.18

Mutation Taster

=96/4

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over