11-48144715-G-T

Variant names:

• chr11-48144715-G-T
• rs4752904
• NM_002843.4:c.2616G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002843.4(PTPRJ):​c.2616G>T​(p.Glu872Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98
• Publications: 44 publications found

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 Gene-Disease associations (from GenCC):

• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• thrombocytopenia 10

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, ClinGen
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018011957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	NM_002843.4	MANE Select	c.2616G>T	p.Glu872Asp	missense	Exon 13 of 25	NP_002834.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.2616G>T	p.Glu872Asp	missense	Exon 13 of 25	ENSP00000400010.2	Q12913-1
	PTPRJ	ENST00000698881.1		c.2958G>T	p.Glu986Asp	missense	Exon 13 of 25	ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250806 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461754 Hom.: 0 Cov.: 47 AF XY: 0.00000550 AC XY: 4 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111892

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6016

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.012
DANN	Benign	0.26
DEOGEN2	Benign	0.051	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-4.0
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.019
Sift	Benign	0.65	T
Sift4G	Benign	0.53	T
Polyphen		0.0070	B
Vest4		0.032
MutPred		0.21		Gain of sheet (P = 0.0827)
MVP		0.18
MPC		0.21
ClinPred		0.028	T
GERP RS		-11
Varity_R		0.031
gMVP		0.23
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4752904; hg19: chr11-48166267;