11-48143169-T-C

Variant names:

• chr11-48143169-T-C
• rs1566729
• NM_002843.4:c.2575+119T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418331.7(PTPRJ):​c.2575+119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,315,504 control chromosomes in the GnomAD database, including 444,241 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 0.79 (47477 hom., cov: 33)
  • Exomes 𝑓: 0.83 (396764 hom.)
• Consequence: PTPRJ ENST00000418331.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418331.7. 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.2575+119T>C		intron	N/A	NP_002834.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.2575+119T>C		intron	N/A	ENSP00000400010.2
	PTPRJ	ENST00000698881.1		c.2917+119T>C		intron	N/A	ENSP00000514003.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119471 AN: 152062 Hom.: 47446 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.825 AC: 959801 AN: 1163324 Hom.: 396764 AF XY: 0.826 AC XY: 477453 AN XY: 578096

African (AFR) AF: 0.662 AC: 17639 AN: 26634

American (AMR) AF: 0.847 AC: 24345 AN: 28750

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 16400 AN: 19154

East Asian (EAS) AF: 0.846 AC: 31120 AN: 36790

South Asian (SAS) AF: 0.831 AC: 54050 AN: 65020

European-Finnish (FIN) AF: 0.812 AC: 34140 AN: 42060

Middle Eastern (MID) AF: 0.857 AC: 2911 AN: 3398

European-Non Finnish (NFE) AF: 0.827 AC: 737928 AN: 891766

Other (OTH) AF: 0.829 AC: 41268 AN: 49752

GnomAD4 genome AF: 0.786 AC: 119551 AN: 152180 Hom.: 47477 Cov.: 33 AF XY: 0.786 AC XY: 58442 AN XY: 74382

African (AFR) AF: 0.670 AC: 27787 AN: 41494

American (AMR) AF: 0.839 AC: 12833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4389 AN: 5166

South Asian (SAS) AF: 0.840 AC: 4056 AN: 4830

European-Finnish (FIN) AF: 0.798 AC: 8458 AN: 10600

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56258 AN: 68008

Other (OTH) AF: 0.821 AC: 1734 AN: 2112

Alfa AF: 0.820 Hom.: 214729

Bravo AF: 0.786

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-1.0
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: rs1566729; hg19: chr11-48164721;