11-48069751-T-G

Variant names:

• chr11-48069751-T-G
• rs10838798
• NM_002843.4:c.97-40307T>G

Variant summary

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

The ENST00000418331.7(PTPRJ):​c.97-40307T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,106 control chromosomes in the GnomAD database, including 28,526 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 0.57 (28526 hom., cov: 32)
• Consequence: PTPRJ ENST00000418331.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 16 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 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.97-40307T>G		intron	N/A	NP_002834.3
	PTPRJ	NM_001098503.2		c.97-40307T>G		intron	N/A	NP_001091973.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.97-40307T>G		intron	N/A	ENSP00000400010.2
	PTPRJ	ENST00000440289.6	TSL:1	c.97-40307T>G		intron	N/A	ENSP00000409733.2
	PTPRJ	ENST00000698881.1		c.439-40307T>G		intron	N/A	ENSP00000514003.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86733 AN: 151988 Hom.: 28515 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.570 AC: 86761 AN: 152106 Hom.: 28526 Cov.: 32 AF XY: 0.577 AC XY: 42890 AN XY: 74346

African (AFR) AF: 0.220 AC: 9112 AN: 41490

American (AMR) AF: 0.688 AC: 10518 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4157 AN: 5160

South Asian (SAS) AF: 0.770 AC: 3715 AN: 4824

European-Finnish (FIN) AF: 0.710 AC: 7498 AN: 10566

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47043 AN: 67998

Other (OTH) AF: 0.627 AC: 1321 AN: 2108

Alfa AF: 0.635 Hom.: 47162

Bravo AF: 0.556

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.6
DANN	Benign	0.84
PhyloP100		0.21
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: rs10838798; hg19: chr11-48091303;