chr10-127925926-A-G

Variant names:

• chr10-127925926-A-G
• rs1410064
• NM_006504.6:c.-31+18617A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006504.6(PTPRE):​c.-31+18617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,126 control chromosomes in the GnomAD database, including 18,318 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 0.47 (18318 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-31+18617A>G		intron_variant	Intron 1 of 20	ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.-31+18617A>G		intron_variant	Intron 1 of 20	1	NM_006504.6	ENSP00000254667.3
PTPRE	ENST00000442830.5	c.-202+18617A>G		intron_variant	Intron 1 of 6	5		ENSP00000410540.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71321 AN: 152006 Hom.: 18262 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.470 AC: 71430 AN: 152126 Hom.: 18318 Cov.: 32 AF XY: 0.466 AC XY: 34628 AN XY: 74360

African (AFR) AF: 0.695 AC: 28857 AN: 41508

American (AMR) AF: 0.455 AC: 6953 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2022 AN: 5182

South Asian (SAS) AF: 0.468 AC: 2257 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3198 AN: 10570

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25295 AN: 67990

Other (OTH) AF: 0.471 AC: 995 AN: 2114

Alfa AF: 0.422 Hom.: 4197

Bravo AF: 0.493

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.67
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1410064; hg19: chr10-129724190;