NM_002843.4:c.82C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002843.4(PTPRJ):c.82C>G(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,161,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.820

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1060859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_047427374.1 link	c.424C>G	p.Leu142Val	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2 link	c.48+376C>G		intron_variant	Intron 1 of 24		XP_016873574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 link	c.82C>G	p.Leu28Val	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2		Q12913-1

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000604

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1015514

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

478126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21060

American (AMR)

AF:

0.00

AC:

AN:

6408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12126

East Asian (EAS)

AF:

0.00

AC:

AN:

23052

South Asian (SAS)

AF:

0.0000530

AC:

AN:

18858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15464

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2578

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

876360

Other (OTH)

AF:

0.00

AC:

AN:

39608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000273

AC:

AN:

146422

Hom.:

Cov.:

AF XY:

0.0000421

AC XY:

AN XY:

71298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40380

American (AMR)

AF:

0.00

AC:

AN:

14898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

4614

South Asian (SAS)

AF:

0.00

AC:

AN:

4414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.0000604

AC:

AN:

66196

Other (OTH)

AF:

0.00

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.82C>G (p.L28V) alteration is located in exon 1 (coding exon 1) of the PTPRJ gene. This alteration results from a C to G substitution at nucleotide position 82, causing the leucine (L) at amino acid position 28 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.2

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.047

T;T;T;.;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.47

T;T;T;T;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;N;.;N;.;.

PhyloP100

-0.82

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.29

.;N;.;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.20

.;T;.;T;T;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.73

.;P;.;.;.;.

Vest4

0.16

MutPred

0.37

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.31

MPC

0.38

ClinPred

0.18

GERP RS

-2.8

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.048

gMVP

0.090

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_002843.4:c.82C>G

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