10-127997982-T-C

Position:

• chr10-127997982-T-C

Variant summary

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

The NM_006504.6(PTPRE):​c.-8+15686T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,212 control chromosomes in the GnomAD database, including 2,738 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 0.18 (2738 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-8+15686T>C		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+15686T>C		intron_variant		1	NM_006504.6	ENSP00000254667
PTPRE	ENST00000442830.5	c.-8+15686T>C		intron_variant		5		ENSP00000410540
PTPRE	ENST00000471218.5	c.-8+10587T>C		intron_variant		3		ENSP00000474102

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27315 AN: 152092 Hom.: 2738 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.180 AC: 27324 AN: 152212 Hom.: 2738 Cov.: 33 AF XY: 0.185 AC XY: 13780 AN XY: 74404

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.139

Alfa AF: 0.167 Hom.: 4686

Bravo AF: 0.168

Asia WGS AF: 0.295 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.60

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: rs7922288; hg19: chr10-129796246;