rs12049671

Positions:

• chr10-127939367-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.-31+32058C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,180 control chromosomes in the GnomAD database, including 1,871 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 0.15 (1871 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRE	NM_006504.6	c.-31+32058C>T		intron_variant		ENST00000254667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRE	ENST00000254667.8	c.-31+32058C>T		intron_variant		1	NM_006504.6
PTPRE	ENST00000442830.5	c.-201-25461C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22774 AN: 152060 Hom.: 1868 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.150 AC: 22792 AN: 152180 Hom.: 1871 Cov.: 32 AF XY: 0.152 AC XY: 11303 AN XY: 74396

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.157

Alfa AF: 0.154 Hom.: 319

Bravo AF: 0.155

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.64

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: rs12049671; hg19: chr10-129737631;