NM_002843.4:c.406A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002843.4(PTPRJ):c.406A>G(p.Ile136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.0000089 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.237

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030777305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.406A>G	p.Ile136Val	missense_variant	Exon 4 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.406A>G	p.Ile136Val	missense_variant	Exon 4 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_017018085.2 link	c.358A>G	p.Ile120Val	missense_variant	Exon 4 of 25		XP_016873574.1
PTPRJ	XM_047427374.1 link	c.748A>G	p.Ile250Val	missense_variant	Exon 4 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 link	c.406A>G	p.Ile136Val	missense_variant	Exon 4 of 25	1	NM_002843.4	ENSP00000400010.2		Q12913-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250236

AF XY:

0.00000739

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461168

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000900

AC:

AN:

1111552

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.406A>G (p.I136V) alteration is located in exon 4 (coding exon 4) of the PTPRJ gene. This alteration results from a A to G substitution at nucleotide position 406, causing the isoleucine (I) at amino acid position 136 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

-0.33

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.39

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.040

T;T;T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.20

T;T;T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.031

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.49

.;N;.;N;.

PhyloP100

-0.24

PrimateAI

Benign

0.25

PROVEAN

Benign

0.050

.;N;.;N;N

REVEL

Benign

0.041

Sift

Benign

0.41

.;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0050

.;B;.;.;.

Vest4

0.035

MVP

0.072

MPC

0.19

ClinPred

0.031

GERP RS

-6.7

Varity_R

0.027

gMVP

0.084

Mutation Taster

=99/1

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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NM_002843.4:c.406A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over