11-48112873-C-A

Variant names:

• chr11-48112873-C-A
• NM_002843.4:c.242C>A

Variant summary

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

The NM_002843.4(PTPRJ):​c.242C>A​(p.Thr81Lys) 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. 14/21 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: -0.416

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=0.06768218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.242C>A	p.Thr81Lys	missense_variant	Exon 3 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.242C>A	p.Thr81Lys	missense_variant	Exon 3 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.194C>A	p.Thr65Lys	missense_variant	Exon 3 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.584C>A	p.Thr195Lys	missense_variant	Exon 3 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.242C>A	p.Thr81Lys	missense_variant	Exon 3 of 25	1	NM_002843.4	ENSP00000400010.2

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

not specified Uncertain:1

Dec 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.242C>A (p.T81K) alteration is located in exon 3 (coding exon 3) of the PTPRJ gene. This alteration results from a C to A substitution at nucleotide position 242, causing the threonine (T) at amino acid position 81 to be replaced by a lysine (K). 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	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.2
DANN	Benign	0.71
DEOGEN2	Benign	0.064	T;T;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.51	T;T;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.068	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;.;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.73	.;N;.;N;D
REVEL	Benign	0.035
Sift	Benign	0.15	.;T;.;T;D
Sift4G	Benign	0.33	T;T;T;T;D
Polyphen		0.60	.;P;.;.;.
Vest4		0.27
MutPred		0.40		Gain of ubiquitination at T81 (P = 6e-04);Gain of ubiquitination at T81 (P = 6e-04);Gain of ubiquitination at T81 (P = 6e-04);Gain of ubiquitination at T81 (P = 6e-04);Gain of ubiquitination at T81 (P = 6e-04);
MVP		0.25
MPC		0.28
ClinPred		0.086	T
GERP RS		-0.49
Varity_R		0.048
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-48134425;