chr11-48125070-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002843.4(PTPRJ):c.977G>A(p.Arg326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,764 control chromosomes in the GnomAD database, including 25,135 homozygotes. 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 Lovd as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2919 hom., cov: 31)

Exomes 𝑓: 0.17 ( 22216 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.74

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004000932).

BP6

Variant 11-48125070-G-A is Benign according to our data. Variant chr11-48125070-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 9		NP_001091973.1	Q12913-2
PTPRJ	XM_017018085.2 link	c.929G>A	p.Arg310Gln	missense_variant	Exon 6 of 25		XP_016873574.1
PTPRJ	XM_047427374.1 link	c.1319G>A	p.Arg440Gln	missense_variant	Exon 6 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRJ	ENST00000418331.7 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 25	1	NM_002843.4	ENSP00000400010.2	Q12913-1
PTPRJ	ENST00000440289.6 link	c.977G>A	p.Arg326Gln	missense_variant	Exon 6 of 9	1		ENSP00000409733.2	Q12913-2
PTPRJ	ENST00000698881.1 link	c.1319G>A	p.Arg440Gln	missense_variant	Exon 6 of 25			ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28559

AN:

151816

Hom.:

2918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.0992

Gnomad MID

AF:

0.240

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.178

AC:

44759

AN:

251382

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.169

AC:

246521

AN:

1461830

Hom.:

22216

Cov.:

AF XY:

0.172

AC XY:

125146

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.251

AC:

8401

AN:

33480

Gnomad4 AMR exome

AF:

0.109

AC:

4877

AN:

44724

Gnomad4 ASJ exome

AF:

0.240

AC:

6278

AN:

26136

Gnomad4 EAS exome

AF:

0.241

AC:

9553

AN:

39700

Gnomad4 SAS exome

AF:

0.266

AC:

22970

AN:

86258

Gnomad4 FIN exome

AF:

0.0995

AC:

5313

AN:

53390

Gnomad4 NFE exome

AF:

0.158

AC:

175950

AN:

1111980

Gnomad4 Remaining exome

AF:

0.192

AC:

11588

AN:

60394

Heterozygous variant carriers

13434

26868

40303

53737

67171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

6420

12840

19260

25680

32100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28577

AN:

151934

Hom.:

2919

Cov.:

AF XY:

0.187

AC XY:

13864

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.248

AC:

0.247813

AN:

0.247813

Gnomad4 AMR

AF:

0.160

AC:

0.160492

AN:

0.160492

Gnomad4 ASJ

AF:

0.238

AC:

0.238329

AN:

0.238329

Gnomad4 EAS

AF:

0.275

AC:

0.275078

AN:

0.275078

Gnomad4 SAS

AF:

0.246

AC:

0.246467

AN:

0.246467

Gnomad4 FIN

AF:

0.0992

AC:

0.0991673

AN:

0.0991673

Gnomad4 NFE

AF:

0.159

AC:

0.158909

AN:

0.158909

Gnomad4 OTH

AF:

0.202

AC:

0.202471

AN:

0.202471

Heterozygous variant carriers

1170

2340

3511

4681

5851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.175

Hom.:

11337

Bravo

AF:

0.194

TwinsUK

AF:

0.155

AC:

576

ALSPAC

AF:

0.149

AC:

576

ESP6500AA

AF:

0.252

AC:

1111

ESP6500EA

AF:

0.161

AC:

1387

ExAC

AF:

0.180

AC:

21919

Asia WGS

AF:

0.253

AC:

880

AN:

3478

EpiCase

AF:

0.181

EpiControl

AF:

0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.0030

DANN

Benign

0.50

DEOGEN2

Benign

0.045

T;T;T;.

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.31

T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.32

.;N;.;N

PrimateAI

Benign

0.18

PROVEAN

Benign

0.58

.;N;.;N

REVEL

Benign

0.042

Sift

Benign

0.49

.;T;.;T

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.041

MPC

0.26

ClinPred

0.0065

GERP RS

-10

Varity_R

0.013

gMVP

0.14

Mutation Taster

=100/0

polymorphism (auto)

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over