rs11016002

Variant names:

• chr10-127992540-T-A
• rs11016002
• NM_006504.6:c.-8+10244T>A

Variant summary

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

The NM_006504.6(PTPRE):​c.-8+10244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,048 control chromosomes in the GnomAD database, including 38,338 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 0.70 (38338 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-8+10244T>A		intron_variant	Intron 2 of 20	ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.-8+10244T>A		intron_variant	Intron 2 of 20	1	NM_006504.6	ENSP00000254667.3
PTPRE	ENST00000471218.5	c.-8+5145T>A		intron_variant	Intron 1 of 5	3		ENSP00000474102.1
PTPRE	ENST00000442830.5	c.-8+10244T>A		intron_variant	Intron 3 of 6	5		ENSP00000410540.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106903 AN: 151930 Hom.: 38282 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.704 AC: 107012 AN: 152048 Hom.: 38338 Cov.: 32 AF XY: 0.704 AC XY: 52344 AN XY: 74306

African (AFR) AF: 0.857 AC: 35576 AN: 41514

American (AMR) AF: 0.650 AC: 9925 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2081 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3148 AN: 5146

South Asian (SAS) AF: 0.658 AC: 3175 AN: 4828

European-Finnish (FIN) AF: 0.688 AC: 7257 AN: 10554

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.641 AC: 43564 AN: 67956

Other (OTH) AF: 0.650 AC: 1371 AN: 2108

Alfa AF: 0.680 Hom.: 4449

Bravo AF: 0.709

Asia WGS AF: 0.622 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.69
PhyloP100		-0.78
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: rs11016002; hg19: chr10-129790804;