NM_002843.4:c.19G>T

Variant names:

• chr11-47980931-G-T
• rs1246834189
• NM_002843.4:c.19G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002843.4(PTPRJ):​c.19G>T​(p.Glu7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000965 in 1,035,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 9.7e-7 (0 hom.)
• Consequence: PTPRJ NM_002843.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.19G>T	p.Glu7*	stop_gained	Exon 1 of 25	NP_002834.3
	PTPRJ	NM_001098503.2		c.19G>T	p.Glu7*	stop_gained	Exon 1 of 9	NP_001091973.1	Q12913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 25	ENSP00000400010.2	Q12913-1
	PTPRJ	ENST00000440289.6	TSL:1	c.19G>T	p.Glu7*	stop_gained	Exon 1 of 9	ENSP00000409733.2	Q12913-2
	PTPRJ	ENST00000698881.1		c.361G>T	p.Glu121*	stop_gained	Exon 1 of 25	ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.65e-7 AC: 1 AN: 1035870 Hom.: 0 Cov.: 30 AF XY: 0.00000205 AC XY: 1 AN XY: 488624

African (AFR) AF: 0.00 AC: 0 AN: 21148

American (AMR) AF: 0.00 AC: 0 AN: 6882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12206

East Asian (EAS) AF: 0.00 AC: 0 AN: 22458

South Asian (SAS) AF: 0.00 AC: 0 AN: 19148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2674

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 891740

Other (OTH) AF: 0.00 AC: 0 AN: 40264

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.41	N
PhyloP100		0.11
Vest4		0.48
GERP RS		3.4
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=15/185	disease causing (fs/PTC)

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: rs1246834189; hg19: chr11-48002483;