chr11-48123823-A-C

Position:

chr11-48123823-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002843.4(PTPRJ):c.827A>C(p.Gln276Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,772 control chromosomes in the GnomAD database, including 23,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1847 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21299 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: 0.0800

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005792141).

BP6

Variant 11-48123823-A-C is Benign according to our data. Variant chr11-48123823-A-C is described in ClinVar as [Benign]. Clinvar id is 8690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-48123823-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4 linkuse as main transcript	c.827A>C	p.Gln276Pro	missense_variant	5/25	ENST00000418331.7	NP_002834.3	Q12913-1Q9NPR5
PTPRJ	NM_001098503.2 linkuse as main transcript	c.827A>C	p.Gln276Pro	missense_variant	5/9		NP_001091973.1	Q12913-2
PTPRJ	XM_017018085.2 linkuse as main transcript	c.779A>C	p.Gln260Pro	missense_variant	5/25		XP_016873574.1
PTPRJ	XM_047427374.1 linkuse as main transcript	c.1169A>C	p.Gln390Pro	missense_variant	5/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPRJ	ENST00000418331.7 linkuse as main transcript	c.827A>C	p.Gln276Pro	missense_variant	5/25	1	NM_002843.4	ENSP00000400010.2	Q12913-1
PTPRJ	ENST00000440289.6 linkuse as main transcript	c.827A>C	p.Gln276Pro	missense_variant	5/9	1		ENSP00000409733.2	Q12913-2
PTPRJ	ENST00000698881.1 linkuse as main transcript	c.1169A>C	p.Gln390Pro	missense_variant	5/25			ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23059

AN:

152020

Hom.:

1848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.0990

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.169

AC:

42380

AN:

251292

Hom.:

4138

AF XY:

0.179

AC XY:

24256

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0970

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.165

AC:

241340

AN:

1461634

Hom.:

21299

Cov.:

AF XY:

0.169

AC XY:

122945

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.0997

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.152

AC:

23056

AN:

152138

Hom.:

1847

Cov.:

AF XY:

0.152

AC XY:

11286

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.237

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.248

Gnomad4 FIN

AF:

0.0990

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.171

Hom.:

4769

Bravo

AF:

0.152

TwinsUK

AF:

0.155

AC:

573

ALSPAC

AF:

0.149

AC:

574

ESP6500AA

AF:

0.120

AC:

528

ESP6500EA

AF:

0.162

AC:

1389

ExAC

AF:

0.169

AC:

20522

Asia WGS

AF:

0.245

AC:

851

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.187

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -
Benign, criteria provided, single submitter	research	H3Africa Consortium	Oct 28, 2020	While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.063, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Carcinoma of colon

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2002

- -

Colorectal cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 10, 2021

- -

PTPRJ-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.7

DANN

Benign

0.47

DEOGEN2

Benign

0.089

T;T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.36

T;T;T;T

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

.;L;.;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.21

.;N;.;N

REVEL

Benign

0.014

Sift

Benign

0.24

.;T;.;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.0010

.;B;.;.

Vest4

0.21

MPC

0.33

ClinPred

0.0040

GERP RS

1.5

Varity_R

0.087

gMVP

0.76

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over