11-48112913-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002843.4(PTPRJ):c.282T>C(p.Asp94=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,152 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (8 hom.)
• Consequence: PTPRJ NM_002843.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-48112913-T-C is Benign according to our data. Variant chr11-48112913-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2641771.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-48112913-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.63 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRJ	NM_002843.4	c.282T>C	p.Asp94=	synonymous_variant	3/25	ENST00000418331.7
PTPRJ	NM_001098503.2	c.282T>C	p.Asp94=	synonymous_variant	3/9
PTPRJ	XM_017018085.2	c.234T>C	p.Asp78=	synonymous_variant	3/25
PTPRJ	XM_047427374.1	c.624T>C	p.Asp208=	synonymous_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRJ	ENST00000418331.7	c.282T>C	p.Asp94=	synonymous_variant	3/25	1	NM_002843.4	P2

Frequencies

GnomAD3 genomes AF: 0.000927 AC: 141 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00124 AC: 311 AN: 251350 Hom.: 1 AF XY: 0.00122 AC XY: 166 AN XY: 135834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00180 AC: 2632 AN: 1461880 Hom.: 8 Cov.: 31 AF XY: 0.00178 AC XY: 1297 AN XY: 727242

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.000973

Gnomad4 NFE exome AF: 0.00213

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.000926 AC: 141 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000873 AC XY: 65 AN XY: 74454

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00154 Hom.: 0

Bravo AF: 0.000994

EpiCase AF: 0.00174

EpiControl AF: 0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

PTPRJ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.16
Dann	Benign	0.30

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: rs142849806; hg19: chr11-48134465;