11-48143169-T-C

Position:

• chr11-48143169-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002843.4(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 NM_002843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.2575+119T>C		intron_variant		ENST00000418331.7	NP_002834.3
PTPRJ	XM_017018085.2	c.2527+119T>C		intron_variant			XP_016873574.1
PTPRJ	XM_047427374.1	c.2917+119T>C		intron_variant			XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.2575+119T>C		intron_variant		1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000698881.1	c.2917+119T>C		intron_variant				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

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.829

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

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.821

Alfa AF: 0.828 Hom.: 105628

Bravo AF: 0.786

Asia WGS AF: 0.849 AC: 2953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1566729; hg19: chr11-48164721;