11-47980931-G-C

Variant names:

• chr11-47980931-G-C
• rs1246834189
• NM_002843.4:c.19G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002843.4(PTPRJ):​c.19G>C​(p.Glu7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000965 in 1,035,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: PTPRJ NM_002843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 0 publications found

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]

PTPRJ Gene-Disease associations (from GenCC):

• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• thrombocytopenia 10

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1935541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRJ	NM_002843.4	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 25	ENST00000418331.7	NP_002834.3
PTPRJ	NM_001098503.2	c.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 9		NP_001091973.1
PTPRJ	XM_047427374.1	c.361G>C	p.Glu121Gln	missense_variant	Exon 1 of 17		XP_047283330.1
PTPRJ	XM_017018085.2	c.48+313G>C		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.19G>C	p.Glu7Gln	missense_variant	Exon 1 of 25	1	NM_002843.4	ENSP00000400010.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.65e-7 AC: 1 AN: 1035870 Hom.: 0 Cov.: 30 AF XY: 0.00000205 AC XY: 1 AN XY: 488624

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21148

American (AMR) AF: 0.00 AC: 0 AN: 6882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12206

East Asian (EAS) AF: 0.0000445 AC: 1 AN: 22458

South Asian (SAS) AF: 0.00 AC: 0 AN: 19148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 891740

Other (OTH) AF: 0.00 AC: 0 AN: 40264

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;T;T;.;.;T
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.53	T;T;T;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;N;.;.
PhyloP100		0.11
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.77	.;N;.;N;N;N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	.;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.81	.;P;.;.;.;.
Vest4		0.11
MutPred		0.39		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.56
MPC		0.42
ClinPred		0.24	T
GERP RS		3.4
PromoterAI		0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.31
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1246834189; hg19: chr11-48002483;