chr11-48123616-C-T

Position:

chr11-48123616-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000418331.7(PTPRJ):c.620C>T(p.Pro207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,611,922 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

PTPRJ
ENST00000418331.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37645647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PTPRJ	NM_002843.4 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	5/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	5/9		NP_001091973.1
PTPRJ	XM_017018085.2 linkuse as main transcript	c.572C>T	p.Pro191Leu	missense_variant	5/25		XP_016873574.1
PTPRJ	XM_047427374.1 linkuse as main transcript	c.962C>T	p.Pro321Leu	missense_variant	5/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	5/25	1	NM_002843.4	ENSP00000400010	P2	Q12913-1
PTPRJ	ENST00000440289.6 linkuse as main transcript	c.620C>T	p.Pro207Leu	missense_variant	5/9	1		ENSP00000409733		Q12913-2
PTPRJ	ENST00000698881.1 linkuse as main transcript	c.962C>T	p.Pro321Leu	missense_variant	5/25			ENSP00000514003	A2
PTPRJ	ENST00000527952.1 linkuse as main transcript	c.356C>T	p.Pro119Leu	missense_variant	4/4	5		ENSP00000435618

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

250176

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000480

AC:

AN:

1459838

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000496

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.620C>T (p.P207L) alteration is located in exon 5 (coding exon 5) of the PTPRJ gene. This alteration results from a C to T substitution at nucleotide position 620, causing the proline (P) at amino acid position 207 to be replaced by a leucine (L). 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

0.62

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T;.;T

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.054

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.83

T;T;T;T;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

.;M;.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.8

.;D;.;D;D

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

.;D;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.60

MVP

0.71

MPC

0.28

ClinPred

0.50

GERP RS

4.9

Varity_R

0.34

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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