rs61739179

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 211973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-48127939-G-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4 linkuse as main transcript	c.1253G>A	p.Arg418His	missense_variant	7/25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 linkuse as main transcript	c.1253G>A	p.Arg418His	missense_variant	7/9		NP_001091973.1	Q12913-2
PTPRJ	XM_017018085.2 linkuse as main transcript	c.1205G>A	p.Arg402His	missense_variant	7/25		XP_016873574.1
PTPRJ	XM_047427374.1 linkuse as main transcript	c.1595G>A	p.Arg532His	missense_variant	7/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPRJ	ENST00000418331.7 linkuse as main transcript	c.1253G>A	p.Arg418His	missense_variant	7/25	1	NM_002843.4	ENSP00000400010.2	Q12913-1
PTPRJ	ENST00000440289.6 linkuse as main transcript	c.1253G>A	p.Arg418His	missense_variant	7/9	1		ENSP00000409733.2	Q12913-2
PTPRJ	ENST00000698881.1 linkuse as main transcript	c.1595G>A	p.Arg532His	missense_variant	7/25			ENSP00000514003.1	A0A8V8TP51

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

GnomAD3 exomes

AF:

0.00593

AC:

1491

AN:

251392

Hom.:

AF XY:

0.00586

AC XY:

796

AN XY:

135874

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 SAS exome

AF:

0.000653

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

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000765

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.00597

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152226

Hom.:

Cov.:

AF XY:

0.00641

AC XY:

477

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.00788

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00586

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PTPRJ: BP4, BS2 -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 02, 2015

- -

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

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

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

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