rs61739179

chr11-48127939-G-Achr11-48127939-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002843.4(PTPRJ):c.1253G>A(p.Arg418His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,614,106 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R418C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0059 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (59 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.24

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035292208).
• BP6: Variant 11-48127939-G-A is Benign according to our data. Variant chr11-48127939-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-48127939-G-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRJ	NM_002843.4	c.1253G>A	p.Arg418His	missense_variant	7/25	ENST00000418331.7
PTPRJ	NM_001098503.2	c.1253G>A	p.Arg418His	missense_variant	7/9
PTPRJ	XM_017018085.2	c.1205G>A	p.Arg402His	missense_variant	7/25
PTPRJ	XM_047427374.1	c.1595G>A	p.Arg532His	missense_variant	7/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRJ	ENST00000418331.7	c.1253G>A	p.Arg418His	missense_variant	7/25	1	NM_002843.4	P2
PTPRJ	ENST00000440289.6	c.1253G>A	p.Arg418His	missense_variant	7/9	1
PTPRJ	ENST00000698881.1	c.1595G>A	p.Arg532His	missense_variant	7/25			A2

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152108 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00788

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00593 AC: 1491 AN: 251392 Hom.: 25 AF XY: 0.00586 AC XY: 796 AN XY: 135874

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0290

Gnomad NFE exome AF: 0.00667

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00581 AC: 8493 AN: 1461880 Hom.: 59 Cov.: 32 AF XY: 0.00582 AC XY: 4234 AN XY: 727242

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.000805

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.00597

Gnomad4 OTH exome AF: 0.00505

GnomAD4 genome AF: 0.00587 AC: 894 AN: 152226 Hom.: 5 Cov.: 32 AF XY: 0.00641 AC XY: 477 AN XY: 74414

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.00788

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00586 Hom.: 9

Bravo AF: 0.00374

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00617 AC: 53

ExAC AF: 0.00564 AC: 685

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00462

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 02, 2015

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

PTPRJ: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.0020
Dann	Benign	0.80
DEOGEN2	Benign	0.059	T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.30	T;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.19	T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.0070	.;B;.;.
Vest4		0.057
MVP		0.23
MPC		0.29
ClinPred		0.0037	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.18

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

Other links and lift over

dbSNP: rs61739179; hg19: chr11-48149491;