11-48123695-T-C

Variant names:

• chr11-48123695-T-C
• rs2270992
• NM_002843.4:c.699T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002843.4(PTPRJ):​c.699T>C​(p.Thr233Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,613,810 control chromosomes in the GnomAD database, including 278,053 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 0.49 (20815 hom., cov: 31)
  • Exomes 𝑓: 0.59 (257238 hom.)
• Consequence: PTPRJ NM_002843.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.406 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.699T>C	p.Thr233Thr	synonymous_variant	Exon 5 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.699T>C	p.Thr233Thr	synonymous_variant	Exon 5 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.651T>C	p.Thr217Thr	synonymous_variant	Exon 5 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.1041T>C	p.Thr347Thr	synonymous_variant	Exon 5 of 17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.699T>C	p.Thr233Thr	synonymous_variant	Exon 5 of 25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000440289.6	c.699T>C	p.Thr233Thr	synonymous_variant	Exon 5 of 9	1		ENSP00000409733.2
PTPRJ	ENST00000698881.1	c.1041T>C	p.Thr347Thr	synonymous_variant	Exon 5 of 25			ENSP00000514003.1
PTPRJ	ENST00000527952.1	c.435T>C	p.Thr145Thr	synonymous_variant	Exon 4 of 4	5		ENSP00000435618.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74238 AN: 151914 Hom.: 20802 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.505

GnomAD3 exomes AF: 0.580 AC: 145810 AN: 251306 Hom.: 44137 AF XY: 0.579 AC XY: 78657 AN XY: 135826

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.705

Gnomad ASJ exome AF: 0.563

Gnomad EAS exome AF: 0.528

Gnomad SAS exome AF: 0.531

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.607

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.588 AC: 859836 AN: 1461778 Hom.: 257238 Cov.: 61 AF XY: 0.587 AC XY: 427067 AN XY: 727190

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.601

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.488 AC: 74266 AN: 152032 Hom.: 20815 Cov.: 31 AF XY: 0.492 AC XY: 36576 AN XY: 74314

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.509

Alfa AF: 0.549 Hom.: 10444

Bravo AF: 0.477

Asia WGS AF: 0.527 AC: 1832 AN: 3476

EpiCase AF: 0.591

EpiControl AF: 0.588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs2270992; hg19: chr11-48145247; COSMIC: COSV69253155; COSMIC: COSV69253155;