chr11-48121044-C-G

Variant names:

• chr11-48121044-C-G
• NM_002843.4:c.394C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002843.4(PTPRJ):​c.394C>G​(p.Pro132Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.377
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12904021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.394C>G	p.Pro132Ala	missense_variant	Exon 4 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.394C>G	p.Pro132Ala	missense_variant	Exon 4 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.346C>G	p.Pro116Ala	missense_variant	Exon 4 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.736C>G	p.Pro246Ala	missense_variant	Exon 4 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.394C>G	p.Pro132Ala	missense_variant	Exon 4 of 25	1	NM_002843.4	ENSP00000400010.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.394C>G (p.P132A) alteration is located in exon 4 (coding exon 4) of the PTPRJ gene. This alteration results from a C to G substitution at nucleotide position 394, causing the proline (P) at amino acid position 132 to be replaced by an alanine (A). 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	Benign	0.17
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.70
DEOGEN2	Benign	0.081	T;T;T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.75	T;T;T;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.80	.;N;.;N;.
PhyloP100		0.38
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	.;N;.;N;N
REVEL	Benign	0.095
Sift	Benign	0.073	.;T;.;T;T
Sift4G	Benign	0.39	T;T;T;D;T
Polyphen		0.70	.;P;.;.;.
Vest4		0.20
MutPred		0.44		Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);Gain of MoRF binding (P = 0.0665);.;
MVP		0.61
MPC		0.24
ClinPred		0.14	T
GERP RS		-1.6
Varity_R		0.084
gMVP		0.16
Mutation Taster		=98/2	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

hg19: chr11-48142596;