chr11-47980928-C-T

Variant names:

• chr11-47980928-C-T
• rs1284090096
• NM_002843.4:c.16C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002843.4(PTPRJ):​c.16C>T​(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000594 in 1,010,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.533
• 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
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23597202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 9		NP_001091973.1
PTPRJ	XM_047427374.1	c.358C>T	p.Arg120Trp	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2	c.48+310C>T		intron_variant	Intron 1 of 24		XP_016873574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.16C>T	p.Arg6Trp	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000594 AC: 6 AN: 1010804 Hom.: 0 Cov.: 31 AF XY: 0.00000631 AC XY: 3 AN XY: 475586

African (AFR) AF: 0.00 AC: 0 AN: 20450

American (AMR) AF: 0.00 AC: 0 AN: 6080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11352

East Asian (EAS) AF: 0.00 AC: 0 AN: 20668

South Asian (SAS) AF: 0.00 AC: 0 AN: 18874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2550

European-Non Finnish (NFE) AF: 0.00000685 AC: 6 AN: 875384

Other (OTH) AF: 0.00 AC: 0 AN: 38570

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16C>T (p.R6W) alteration is located in exon 1 (coding exon 1) of the PTPRJ gene. This alteration results from a C to T substitution at nucleotide position 16, causing the arginine (R) at amino acid position 6 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T;T;.;.;T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.69	T;T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	.;N;.;N;.;.
PhyloP100		0.53
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	.;N;.;N;N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	.;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.24
MutPred		0.55		Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);
MVP		0.55
MPC		0.63
ClinPred		0.78	D
GERP RS		-0.64
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.35
Mutation Taster		=93/7	polymorphism

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: rs1284090096; hg19: chr11-48002480;