11-48112803-A-T

Position:

• chr11-48112803-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002843.4(PTPRJ):​c.172A>T​(p.Ile58Leu) 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. 15/21 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: -0.0300

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04581201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.172A>T	p.Ile58Leu	missense_variant	3/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.172A>T	p.Ile58Leu	missense_variant	3/9		NP_001091973.1
PTPRJ	XM_017018085.2	c.124A>T	p.Ile42Leu	missense_variant	3/25		XP_016873574.1
PTPRJ	XM_047427374.1	c.514A>T	p.Ile172Leu	missense_variant	3/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.172A>T	p.Ile58Leu	missense_variant	3/25	1	NM_002843.4	ENSP00000400010	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

PTPRJ-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2022

The PTPRJ c.172A>T variant is predicted to result in the amino acid substitution p.Ile58Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.021
DANN	Benign	0.39
DEOGEN2	Benign	0.044	T;T;T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00071	N
LIST_S2	Benign	0.36	T;T;T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.046	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.010	.;N;.;N;N
REVEL	Benign	0.086
Sift	Benign	0.51	.;T;.;T;T
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.0	.;B;.;.;.
Vest4		0.076
MutPred		0.11		Loss of glycosylation at T59 (P = 0.1098);Loss of glycosylation at T59 (P = 0.1098);Loss of glycosylation at T59 (P = 0.1098);Loss of glycosylation at T59 (P = 0.1098);Loss of glycosylation at T59 (P = 0.1098);
MVP		0.15
MPC		0.23
ClinPred		0.022	T
GERP RS		-2.5
Varity_R		0.037
gMVP		0.092

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-48134355;