rs1566734

chr11-48123823-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002843.4(PTPRJ):c.827A>C(p.Gln276Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,772 control chromosomes in the GnomAD database, including 23,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1847 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21299 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: 0.0800

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005792141).
• BP6: Variant 11-48123823-A-C is Benign according to our data. Variant chr11-48123823-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 8690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-48123823-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRJ	NM_002843.4	c.827A>C	p.Gln276Pro	missense_variant	5/25	ENST00000418331.7
PTPRJ	NM_001098503.2	c.827A>C	p.Gln276Pro	missense_variant	5/9
PTPRJ	XM_017018085.2	c.779A>C	p.Gln260Pro	missense_variant	5/25
PTPRJ	XM_047427374.1	c.1169A>C	p.Gln390Pro	missense_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRJ	ENST00000418331.7	c.827A>C	p.Gln276Pro	missense_variant	5/25	1	NM_002843.4	P2
PTPRJ	ENST00000440289.6	c.827A>C	p.Gln276Pro	missense_variant	5/9	1
PTPRJ	ENST00000698881.1	c.1169A>C	p.Gln390Pro	missense_variant	5/25			A2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23059 AN: 152020 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.169 AC: 42380 AN: 251292 Hom.: 4138 AF XY: 0.179 AC XY: 24256 AN XY: 135814

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0970

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.276

Gnomad SAS exome AF: 0.267

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.165 AC: 241340 AN: 1461634 Hom.: 21299 Cov.: 35 AF XY: 0.169 AC XY: 122945 AN XY: 727154

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.0997

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.152 AC: 23056 AN: 152138 Hom.: 1847 Cov.: 32 AF XY: 0.152 AC XY: 11286 AN XY: 74380

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.179

Alfa AF: 0.171 Hom.: 4769

Bravo AF: 0.152

TwinsUK AF: 0.155 AC: 573

ALSPAC AF: 0.149 AC: 574

ESP6500AA AF: 0.120 AC: 528

ESP6500EA AF: 0.162 AC: 1389

ExAC AF: 0.169 AC: 20522

Asia WGS AF: 0.245 AC: 851 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.187

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	research	H3Africa Consortium	Oct 28, 2020	While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.063, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Carcinoma of colon Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2002

- -

Colorectal cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 10, 2021

- -

PTPRJ-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	1.7
Dann	Benign	0.47
DEOGEN2	Benign	0.089	T;T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.36	T;T;T;T
MetaRNN	Benign	0.0058	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.21
MPC		0.33
ClinPred		0.0040	T
GERP RS		1.5
Varity_R		0.087
gMVP		0.76

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: rs1566734; hg19: chr11-48145375; COSMIC: COSV69249563; COSMIC: COSV69249563;