11-47980997-C-A

Variant names:

• chr11-47980997-C-A
• rs1853887524
• NM_002843.4:c.85C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002843.4(PTPRJ):​c.85C>A​(p.Arg29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10546118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 9		NP_001091973.1
PTPRJ	XM_047427374.1	c.427C>A	p.Arg143Ser	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2	c.48+379C>A		intron_variant	Intron 1 of 24		XP_016873574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRJ	ENST00000418331.7	c.85C>A	p.Arg29Ser	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1050798 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 496168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.6
DANN	Benign	0.92
DEOGEN2	Benign	0.045	T;T;T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.41	T;T;T;T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;N;.;N;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.53	.;N;.;N;N;N
REVEL	Benign	0.034
Sift	Pathogenic	0.0	.;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.25	.;B;.;.;.;.
Vest4		0.11
MutPred		0.55		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.27
MPC		0.50
ClinPred		0.13	T
GERP RS		1.2
Varity_R		0.15
gMVP		0.19

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: rs1853887524; hg19: chr11-48002549;