Variant 11-48112761-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002843.4(PTPRJ):c.130C>A(p.Pro44Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.913

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039649844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTPRJ	NM_002843.4 linkuse as main transcript	c.130C>A	p.Pro44Thr	missense_variant	3/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2 linkuse as main transcript	c.130C>A	p.Pro44Thr	missense_variant	3/9		NP_001091973.1
PTPRJ	XM_017018085.2 linkuse as main transcript	c.82C>A	p.Pro28Thr	missense_variant	3/25		XP_016873574.1
PTPRJ	XM_047427374.1 linkuse as main transcript	c.472C>A	p.Pro158Thr	missense_variant	3/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 linkuse as main transcript	c.130C>A	p.Pro44Thr	missense_variant	3/25	1	NM_002843.4	ENSP00000400010	P2	Q12913-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251338

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461244

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.130C>A (p.P44T) alteration is located in exon 3 (coding exon 3) of the PTPRJ gene. This alteration results from a C to A substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.6

DANN

Benign

0.35

DEOGEN2

Benign

0.045

T;T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.51

T;T;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.080

.;N;.;N;N

REVEL

Benign

0.026

Sift

Benign

0.81

.;T;.;T;T

Sift4G

Benign

0.72

T;T;T;T;T

Polyphen

0.0010

.;B;.;.;.

Vest4

0.058

MutPred

0.32

Gain of phosphorylation at P44 (P = 0.0092);Gain of phosphorylation at P44 (P = 0.0092);Gain of phosphorylation at P44 (P = 0.0092);Gain of phosphorylation at P44 (P = 0.0092);Gain of phosphorylation at P44 (P = 0.0092);

MVP

0.13

MPC

0.26

ClinPred

0.011

GERP RS

0.087

Varity_R

0.025

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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