11-47980931-G-A

Variant names:

• chr11-47980931-G-A
• rs1246834189
• NM_002843.4:c.19G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002843.4(PTPRJ):​c.19G>A​(p.Glu7Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,186,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109
• 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, ClinGen
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18459773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	NM_002843.4	MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 25	NP_002834.3
	PTPRJ	NM_001098503.2		c.19G>A	p.Glu7Lys	missense	Exon 1 of 9	NP_001091973.1	Q12913-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 25	ENSP00000400010.2	Q12913-1
	PTPRJ	ENST00000440289.6	TSL:1	c.19G>A	p.Glu7Lys	missense	Exon 1 of 9	ENSP00000409733.2	Q12913-2
	PTPRJ	ENST00000698881.1		c.361G>A	p.Glu121Lys	missense	Exon 1 of 25	ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes AF: 0.0000399 AC: 6 AN: 150206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000637 AC: 66 AN: 1035870 Hom.: 0 Cov.: 30 AF XY: 0.0000696 AC XY: 34 AN XY: 488624

African (AFR) AF: 0.00 AC: 0 AN: 21148

American (AMR) AF: 0.00 AC: 0 AN: 6882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12206

East Asian (EAS) AF: 0.00 AC: 0 AN: 22458

South Asian (SAS) AF: 0.000157 AC: 3 AN: 19148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2674

European-Non Finnish (NFE) AF: 0.0000684 AC: 61 AN: 891740

Other (OTH) AF: 0.0000497 AC: 2 AN: 40264

GnomAD4 genome AF: 0.0000399 AC: 6 AN: 150206 Hom.: 0 Cov.: 32 AF XY: 0.0000409 AC XY: 3 AN XY: 73308

African (AFR) AF: 0.0000729 AC: 3 AN: 41180

American (AMR) AF: 0.000132 AC: 2 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67332

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.11
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.41	B
Vest4		0.14
MutPred		0.42		Loss of sheet (P = 7e-04)
MVP		0.55
MPC		0.40
ClinPred		0.33	T
GERP RS		3.4
PromoterAI		0.073	Neutral
Varity_R		0.36
gMVP		0.43
Mutation Taster		=88/12	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: rs1246834189; hg19: chr11-48002483;