rs1246834189

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002843.4(PTPRJ):c.19G>A(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,186,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.109

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=0.18459773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_047427374.1 link	c.361G>A	p.Glu121Lys	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2 link	c.48+313G>A		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.19G>A	p.Glu7Lys	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2		Q12913-1

Frequencies

GnomAD3 genomes

AF:

0.0000399

AC:

AN:

150206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000637

AC:

AN:

1035870

Hom.:

Cov.:

AF XY:

0.0000696

AC XY:

AN XY:

488624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21148

American (AMR)

AF:

0.00

AC:

AN:

6882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12206

East Asian (EAS)

AF:

0.00

AC:

AN:

22458

South Asian (SAS)

AF:

0.000157

AC:

AN:

19148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2674

European-Non Finnish (NFE)

AF:

0.0000684

AC:

AN:

891740

Other (OTH)

AF:

0.0000497

AC:

AN:

40264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000399

AC:

AN:

150206

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73308

show subpopulations

African (AFR)

AF:

0.0000729

AC:

AN:

41180

American (AMR)

AF:

0.000132

AC:

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67332

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.19G>A (p.E7K) alteration is located in exon 1 (coding exon 1) of the PTPRJ gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a lysine (K). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;T;.;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.63

T;T;T;T;T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;.;N;.;.

PhyloP100

0.11

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.99

.;N;.;N;N;N

REVEL

Benign

0.087

Sift

Pathogenic

0.0

.;D;.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.41

.;B;.;.;.;.

Vest4

0.14

MutPred

0.42

Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);

MVP

0.55

MPC

0.40

ClinPred

0.33

GERP RS

3.4

PromoterAI

0.073

Neutral

(source)

Varity_R

0.36

gMVP

0.43

Mutation Taster

=88/12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1246834189

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