11-48123796-A-T

Position:

• chr11-48123796-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000418331.7(PTPRJ):​c.800A>T​(p.Gln267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PTPRJ ENST00000418331.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.18

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22271761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.800A>T	p.Gln267Leu	missense_variant	5/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.800A>T	p.Gln267Leu	missense_variant	5/9		NP_001091973.1
PTPRJ	XM_017018085.2	c.752A>T	p.Gln251Leu	missense_variant	5/25		XP_016873574.1
PTPRJ	XM_047427374.1	c.1142A>T	p.Gln381Leu	missense_variant	5/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.800A>T	p.Gln267Leu	missense_variant	5/25	1	NM_002843.4	ENSP00000400010	P2
PTPRJ	ENST00000440289.6	c.800A>T	p.Gln267Leu	missense_variant	5/9	1		ENSP00000409733
PTPRJ	ENST00000698881.1	c.1142A>T	p.Gln381Leu	missense_variant	5/25			ENSP00000514003	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251378 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135844

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.800A>T (p.Q267L) alteration is located in exon 5 (coding exon 5) of the PTPRJ gene. This alteration results from a A to T substitution at nucleotide position 800, causing the glutamine (Q) at amino acid position 267 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0070
DANN	Benign	0.93
DEOGEN2	Benign	0.10	T;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L;.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.5	.;D;.;D
REVEL	Benign	0.044
Sift	Benign	0.14	.;T;.;T
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.0080	.;B;.;.
Vest4		0.17
MutPred		0.48		Loss of ubiquitination at K263 (P = 0.0551);Loss of ubiquitination at K263 (P = 0.0551);Loss of ubiquitination at K263 (P = 0.0551);Loss of ubiquitination at K263 (P = 0.0551);
MVP		0.36
MPC		0.23
ClinPred		0.047	T
GERP RS		-3.1
Varity_R		0.091
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs780296844; hg19: chr11-48145348;