chr11-48125070-G-A

Position:

• chr11-48125070-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002843.4(PTPRJ):​c.977G>A​(p.Arg326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,764 control chromosomes in the GnomAD database, including 25,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (2919 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22216 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.74

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 (MetaRNN=0.004000932).
• BP6: Variant 11-48125070-G-A is Benign according to our data. Variant chr11-48125070-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.977G>A	p.Arg326Gln	missense_variant	6/25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.977G>A	p.Arg326Gln	missense_variant	6/9		NP_001091973.1
PTPRJ	XM_017018085.2	c.929G>A	p.Arg310Gln	missense_variant	6/25		XP_016873574.1
PTPRJ	XM_047427374.1	c.1319G>A	p.Arg440Gln	missense_variant	6/17		XP_047283330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.977G>A	p.Arg326Gln	missense_variant	6/25	1	NM_002843.4	ENSP00000400010	P2
PTPRJ	ENST00000440289.6	c.977G>A	p.Arg326Gln	missense_variant	6/9	1		ENSP00000409733
PTPRJ	ENST00000698881.1	c.1319G>A	p.Arg440Gln	missense_variant	6/25			ENSP00000514003	A2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28559 AN: 151816 Hom.: 2918 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.178 AC: 44759 AN: 251382 Hom.: 4548 AF XY: 0.185 AC XY: 25177 AN XY: 135862

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.274

Gnomad SAS exome AF: 0.266

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.160

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.169 AC: 246521 AN: 1461830 Hom.: 22216 Cov.: 34 AF XY: 0.172 AC XY: 125146 AN XY: 727220

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.0995

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.188 AC: 28577 AN: 151934 Hom.: 2919 Cov.: 31 AF XY: 0.187 AC XY: 13864 AN XY: 74284

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.202

Alfa AF: 0.176 Hom.: 5510

Bravo AF: 0.194

TwinsUK AF: 0.155 AC: 576

ALSPAC AF: 0.149 AC: 576

ESP6500AA AF: 0.252 AC: 1111

ESP6500EA AF: 0.161 AC: 1387

ExAC AF: 0.180 AC: 21919

Asia WGS AF: 0.253 AC: 880 AN: 3478

EpiCase AF: 0.181

EpiControl AF: 0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.50
DEOGEN2	Benign	0.045	T;T;T;.
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.31	T;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.32	.;N;.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.58	.;N;.;N
REVEL	Benign	0.042
Sift	Benign	0.49	.;T;.;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.041
MPC		0.26
ClinPred		0.0065	T
GERP RS		-10
Varity_R		0.013
gMVP		0.14

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: rs1503185; hg19: chr11-48146622; COSMIC: COSV69252306; COSMIC: COSV69252306;