11-48121158-T-C

Position:

chr11-48121158-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002843.4(PTPRJ):c.508T>C(p.Trp170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.58

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022971272).

BP6

Variant 11-48121158-T-C is Benign according to our data. Variant chr11-48121158-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3149457.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTPRJ	NM_002843.4 linkuse as main transcript	c.508T>C	p.Trp170Arg	missense_variant	4/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2 linkuse as main transcript	c.508T>C	p.Trp170Arg	missense_variant	4/9		NP_001091973.1
PTPRJ	XM_017018085.2 linkuse as main transcript	c.460T>C	p.Trp154Arg	missense_variant	4/25		XP_016873574.1
PTPRJ	XM_047427374.1 linkuse as main transcript	c.850T>C	p.Trp284Arg	missense_variant	4/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 linkuse as main transcript	c.508T>C	p.Trp170Arg	missense_variant	4/25	1	NM_002843.4	ENSP00000400010	P2	Q12913-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251276

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0010

DANN

Benign

0.26

DEOGEN2

Benign

0.050

T;T;T;.;.

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.25

T;T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.023

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.76

.;N;.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.10

.;N;.;N;N

REVEL

Benign

0.064

Sift

Benign

0.43

.;T;.;T;T

Sift4G

Benign

0.66

T;T;T;T;T

Polyphen

0.0

.;B;.;.;.

Vest4

0.036

MutPred

0.48

Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);Gain of solvent accessibility (P = 0.0584);.;

MVP

0.27

MPC

0.40

ClinPred

0.021

GERP RS

-11

Varity_R

0.067

gMVP

0.27

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