chr11-48144715-G-C

Position:

• chr11-48144715-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002843.4(PTPRJ):​c.2616G>C​(p.Glu872Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,613,142 control chromosomes in the GnomAD database, including 244,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.44 (18045 hom., cov: 32)
  • Exomes 𝑓: 0.55 (226229 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0584347E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.2616G>C	p.Glu872Asp	missense_variant	13/25	ENST00000418331.7	NP_002834.3
PTPRJ	XM_017018085.2	c.2568G>C	p.Glu856Asp	missense_variant	13/25		XP_016873574.1
PTPRJ	XM_047427374.1	c.2958G>C	p.Glu986Asp	missense_variant	13/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.2616G>C	p.Glu872Asp	missense_variant	13/25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000698881.1	c.2958G>C	p.Glu986Asp	missense_variant	13/25			ENSP00000514003.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67510 AN: 151934 Hom.: 18035 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.468

GnomAD3 exomes AF: 0.525 AC: 131735 AN: 250806 Hom.: 36974 AF XY: 0.523 AC XY: 70898 AN XY: 135526

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.649

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.402

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.555

GnomAD4 exome AF: 0.549 AC: 802106 AN: 1461090 Hom.: 226229 Cov.: 47 AF XY: 0.546 AC XY: 396997 AN XY: 726876

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.638

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.606

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.444 AC: 67531 AN: 152052 Hom.: 18045 Cov.: 32 AF XY: 0.446 AC XY: 33156 AN XY: 74328

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.472

Alfa AF: 0.514 Hom.: 6016

Bravo AF: 0.432

TwinsUK AF: 0.567 AC: 2101

ALSPAC AF: 0.578 AC: 2229

ESP6500AA AF: 0.149 AC: 654

ESP6500EA AF: 0.576 AC: 4952

ExAC AF: 0.515 AC: 62488

EpiCase AF: 0.567

EpiControl AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0090
DANN	Benign	0.27
DEOGEN2	Benign	0.051	T;T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.51	T;T;T
MetaRNN	Benign	0.0000011	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	.;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.31	.;N;.
REVEL	Benign	0.019
Sift	Benign	0.65	.;T;.
Sift4G	Benign	0.53	T;T;T
Polyphen		0.0070	.;B;.
Vest4		0.032
MutPred		0.21		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MPC		0.21
ClinPred		0.020	T
GERP RS		-11
Varity_R		0.031
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4752904; hg19: chr11-48166267; COSMIC: COSV69252857; COSMIC: COSV69252857;