rs1386421417

Variant names:

• chr11-47980920-C-G
• rs1386421417
• NM_002843.4:c.8C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-47980920-C-G
• chr11-47980920-C-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.8C>G​(p.Pro3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,017,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P3L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• 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=0.24085873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 9		NP_001091973.1
PTPRJ	XM_047427374.1	c.350C>G	p.Pro117Arg	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2	c.48+302C>G		intron_variant	Intron 1 of 24		XP_016873574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.8C>G	p.Pro3Arg	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000393 AC: 4 AN: 1017528 Hom.: 0 Cov.: 30 AF XY: 0.00000209 AC XY: 1 AN XY: 479476

African (AFR) AF: 0.00 AC: 0 AN: 20552

American (AMR) AF: 0.00 AC: 0 AN: 6354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11466

East Asian (EAS) AF: 0.00 AC: 0 AN: 20742

South Asian (SAS) AF: 0.00 AC: 0 AN: 18918

European-Finnish (FIN) AF: 0.0000556 AC: 1 AN: 17976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2562

European-Non Finnish (NFE) AF: 0.00000341 AC: 3 AN: 880050

Other (OTH) AF: 0.00 AC: 0 AN: 38908

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T;T;.;.;T
Eigen	Benign	0.078
Eigen_PC	Benign	0.052
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.46	T;T;T;T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	.;N;.;N;.;.
PhyloP100		-0.70
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.1	.;N;.;N;N;N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	.;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.
Vest4		0.14
MutPred		0.45		Gain of MoRF binding (P = 0.006);Gain of MoRF binding (P = 0.006);Gain of MoRF binding (P = 0.006);Gain of MoRF binding (P = 0.006);Gain of MoRF binding (P = 0.006);Gain of MoRF binding (P = 0.006);
MVP		0.61
MPC		0.78
ClinPred		0.74	D
GERP RS		2.5
PromoterAI		0.030	Neutral
Varity_R		0.19
gMVP		0.28
Mutation Taster		=92/8	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: rs1386421417; hg19: chr11-48002472;