chr11-48121225-A-C

Variant names:

• chr11-48121225-A-C
• rs61737868
• NM_002843.4:c.575A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002843.4(PTPRJ):​c.575A>C​(p.Asn192Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 2 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity PTPRJ_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20971048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.575A>C	p.Asn192Thr	missense_variant	Exon 4 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.575A>C	p.Asn192Thr	missense_variant	Exon 4 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.527A>C	p.Asn176Thr	missense_variant	Exon 4 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.917A>C	p.Asn306Thr	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.575A>C	p.Asn192Thr	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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.2
DANN	Benign	0.91
DEOGEN2	Benign	0.20	T;T;T;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.46	T;T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.3	.;M;.;M;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.0	.;D;.;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.010	.;D;.;D;D
Sift4G	Benign	0.065	T;T;T;D;D
Polyphen		0.85	.;P;.;.;.
Vest4		0.13
MutPred		0.45		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;
MVP		0.55
MPC		0.38
ClinPred		0.42	T
GERP RS		-2.6
Varity_R		0.091
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs61737868; hg19: chr11-48142777;