11-48123695-T-C

Variant names:

• chr11-48123695-T-C
• rs2270992
• NM_002843.4:c.699T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002843.4(PTPRJ):​c.699T>C​(p.Thr233Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,810 control chromosomes in the GnomAD database, including 278,053 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (20815 hom., cov: 31)
  • Exomes 𝑓: 0.59 (257238 hom.)
• Consequence: PTPRJ NM_002843.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 20 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
• colorectal cancer

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	NM_002843.4	MANE Select	c.699T>C	p.Thr233Thr	synonymous	Exon 5 of 25	NP_002834.3
	PTPRJ	NM_001098503.2		c.699T>C	p.Thr233Thr	synonymous	Exon 5 of 9	NP_001091973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.699T>C	p.Thr233Thr	synonymous	Exon 5 of 25	ENSP00000400010.2
	PTPRJ	ENST00000440289.6	TSL:1	c.699T>C	p.Thr233Thr	synonymous	Exon 5 of 9	ENSP00000409733.2
	PTPRJ	ENST00000698881.1		c.1041T>C	p.Thr347Thr	synonymous	Exon 5 of 25	ENSP00000514003.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74238 AN: 151914 Hom.: 20802 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.505

GnomAD2 exomes AF: 0.580 AC: 145810 AN: 251306 AF XY: 0.579

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.705

Gnomad ASJ exome AF: 0.563

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.588 AC: 859836 AN: 1461778 Hom.: 257238 Cov.: 61 AF XY: 0.587 AC XY: 427067 AN XY: 727190

African (AFR) AF: 0.184 AC: 6153 AN: 33474

American (AMR) AF: 0.695 AC: 31099 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14742 AN: 26136

East Asian (EAS) AF: 0.572 AC: 22701 AN: 39698

South Asian (SAS) AF: 0.529 AC: 45651 AN: 86252

European-Finnish (FIN) AF: 0.648 AC: 34600 AN: 53410

Middle Eastern (MID) AF: 0.491 AC: 2830 AN: 5764

European-Non Finnish (NFE) AF: 0.601 AC: 668161 AN: 1111926

Other (OTH) AF: 0.561 AC: 33899 AN: 60394

GnomAD4 genome AF: 0.488 AC: 74266 AN: 152032 Hom.: 20815 Cov.: 31 AF XY: 0.492 AC XY: 36576 AN XY: 74314

African (AFR) AF: 0.196 AC: 8111 AN: 41472

American (AMR) AF: 0.605 AC: 9249 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2725 AN: 5146

South Asian (SAS) AF: 0.556 AC: 2671 AN: 4808

European-Finnish (FIN) AF: 0.643 AC: 6791 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40867 AN: 67978

Other (OTH) AF: 0.509 AC: 1075 AN: 2110

Alfa AF: 0.545 Hom.: 10463

Bravo AF: 0.477

Asia WGS AF: 0.527 AC: 1832 AN: 3476

EpiCase AF: 0.591

EpiControl AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.29
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2270992; hg19: chr11-48145247; COSMIC: COSV69253155; COSMIC: COSV69253155;