11-48123616-C-A

Variant names:

• chr11-48123616-C-A
• NM_002843.4:c.620C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002843.4(PTPRJ):​c.620C>A​(p.Pro207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.620C>A	p.Pro207Gln	missense_variant	Exon 5 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.620C>A	p.Pro207Gln	missense_variant	Exon 5 of 9		NP_001091973.1
PTPRJ	XM_017018085.2	c.572C>A	p.Pro191Gln	missense_variant	Exon 5 of 25		XP_016873574.1
PTPRJ	XM_047427374.1	c.962C>A	p.Pro321Gln	missense_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.620C>A	p.Pro207Gln	missense_variant	Exon 5 of 25	1	NM_002843.4	ENSP00000400010.2
PTPRJ	ENST00000440289.6	c.620C>A	p.Pro207Gln	missense_variant	Exon 5 of 9	1		ENSP00000409733.2
PTPRJ	ENST00000698881.1	c.962C>A	p.Pro321Gln	missense_variant	Exon 5 of 25			ENSP00000514003.1
PTPRJ	ENST00000527952.1	c.356C>A	p.Pro119Gln	missense_variant	Exon 4 of 4	5		ENSP00000435618.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459838 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726112

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: 0.00000360

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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	30
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;T;T;.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.7	.;M;.;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.6	.;D;.;D;D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	.;D;.;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	.;D;.;.;.
Vest4		0.51
MutPred		0.68		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);.;
MVP		0.74
MPC		0.58
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.37
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.82		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.82		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-48145168;