rs4002572

Positions:

• chr10-128002591-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006504.6(PTPRE):​c.-8+20295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 150,320 control chromosomes in the GnomAD database, including 20,135 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20135 hom., cov: 30)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

Genes affected

PTPRE (HGNC:9669): (protein tyrosine phosphatase receptor type E) 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. Several alternatively spliced transcript variants of this gene have been reported, at least two of which encode a receptor-type PTP that possesses a short extracellular domain, a single transmembrane region, and two tandem intracytoplasmic catalytic domains; another one encodes a PTP that contains a distinct hydrophilic N-terminus, and thus represents a nonreceptor-type isoform of this PTP. Studies of the similar gene in mice suggested the regulatory roles of this PTP in RAS related signal transduction pathways, cytokine-induced SATA signaling, as well as the activation of voltage-gated K+ channels. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-8+20295C>T		intron_variant		ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.-8+20295C>T		intron_variant		1	NM_006504.6	ENSP00000254667
PTPRE	ENST00000442830.5	c.-8+20295C>T		intron_variant		5		ENSP00000410540
PTPRE	ENST00000455661.5	c.-8+2630C>T		intron_variant		2		ENSP00000416939
PTPRE	ENST00000471218.5	c.-8+15196C>T		intron_variant		3		ENSP00000474102

Frequencies

GnomAD3 genomes AF: 0.518 AC: 77752 AN: 150212 Hom.: 20126 Cov.: 30

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 77792 AN: 150320 Hom.: 20135 Cov.: 30 AF XY: 0.523 AC XY: 38373 AN XY: 73378

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.480

Alfa AF: 0.519 Hom.: 2534

Bravo AF: 0.506

Asia WGS AF: 0.583 AC: 2022 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.47

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: rs4002572; hg19: chr10-129800855; COSMIC: COSV54550839;