NM_002843.4:c.2999+149T>G

Variant names:

• chr11-48147112-T-G
• rs3741410
• NM_002843.4:c.2999+149T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002843.4(PTPRJ):​c.2999+149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 717,440 control chromosomes in the GnomAD database, including 9,918 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3178 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6740 hom.)
• Consequence: PTPRJ NM_002843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	NM_002843.4	MANE Select	c.2999+149T>G		intron	N/A	NP_002834.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.2999+149T>G		intron	N/A	ENSP00000400010.2
	PTPRJ	ENST00000698881.1		c.3341+149T>G		intron	N/A	ENSP00000514003.1
	PTPRJ	ENST00000527026.1	TSL:4	n.135+149T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28772 AN: 152060 Hom.: 3174 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.147 AC: 83072 AN: 565262 Hom.: 6740 AF XY: 0.146 AC XY: 43976 AN XY: 300506

African (AFR) AF: 0.303 AC: 4585 AN: 15126

American (AMR) AF: 0.135 AC: 3675 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 1900 AN: 15466

East Asian (EAS) AF: 0.167 AC: 5561 AN: 33234

South Asian (SAS) AF: 0.144 AC: 7804 AN: 54010

European-Finnish (FIN) AF: 0.176 AC: 6802 AN: 38670

Middle Eastern (MID) AF: 0.120 AC: 257 AN: 2148

European-Non Finnish (NFE) AF: 0.138 AC: 48202 AN: 349396

Other (OTH) AF: 0.143 AC: 4286 AN: 30014

GnomAD4 genome AF: 0.189 AC: 28800 AN: 152178 Hom.: 3178 Cov.: 32 AF XY: 0.191 AC XY: 14190 AN XY: 74410

African (AFR) AF: 0.302 AC: 12518 AN: 41494

American (AMR) AF: 0.134 AC: 2042 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.167 AC: 863 AN: 5178

South Asian (SAS) AF: 0.132 AC: 638 AN: 4820

European-Finnish (FIN) AF: 0.193 AC: 2045 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9758 AN: 68006

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.151 Hom.: 1618

Bravo AF: 0.190

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.087
DANN	Benign	0.31
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs3741410; hg19: chr11-48168664;