11-48123823-A-T

Variant names:

• chr11-48123823-A-T
• rs1566734
• NM_002843.4:c.827A>T

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.827A>T​(p.Gln276Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q276P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• 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=0.09211457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.827A>T	p.Gln276Leu	missense_variant	Exon 5 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.827A>T	p.Gln276Leu	missense_variant	Exon 5 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.779A>T	p.Gln260Leu	missense_variant	Exon 5 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.1169A>T	p.Gln390Leu	missense_variant	Exon 5 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.827A>T	p.Gln276Leu	missense_variant	Exon 5 of 25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000440289.6	c.827A>T	p.Gln276Leu	missense_variant	Exon 5 of 9	1		ENSP00000409733.2
PTPRJ	ENST00000698881.1	c.1169A>T	p.Gln390Leu	missense_variant	Exon 5 of 25			ENSP00000514003.1
PTPRJ	ENST00000527952.1	c.*123A>T		downstream_gene_variant		5		ENSP00000435618.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.0
DANN	Benign	0.79
DEOGEN2	Benign	0.098	T;T;T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.26	T;T;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L;.;L
PhyloP100		0.080
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	.;N;.;N
REVEL	Benign	0.018
Sift	Benign	0.22	.;T;.;T
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.062	.;B;.;.
Vest4		0.14
MutPred		0.45		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.37
MPC		0.24
ClinPred		0.070	T
GERP RS		1.5
Varity_R		0.084
gMVP		0.58
Mutation Taster		=94/6	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: rs1566734; hg19: chr11-48145375;