10-127992576-C-T

Variant names:

• chr10-127992576-C-T
• rs7911506
• NM_006504.6:c.-8+10280C>T

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+10280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,036 control chromosomes in the GnomAD database, including 8,092 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 0.32 (8092 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006504.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	NM_006504.6	MANE Select	c.-8+10280C>T		intron	N/A	NP_006495.1
	PTPRE	NM_001323355.2		c.54-48299C>T		intron	N/A	NP_001310284.1
	PTPRE	NM_001323356.2		c.54-48299C>T		intron	N/A	NP_001310285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.-8+10280C>T		intron	N/A	ENSP00000254667.3
	PTPRE	ENST00000471218.5	TSL:3	c.-8+5181C>T		intron	N/A	ENSP00000474102.1
	PTPRE	ENST00000442830.5	TSL:5	c.-8+10280C>T		intron	N/A	ENSP00000410540.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48889 AN: 151918 Hom.: 8091 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.322 AC: 48908 AN: 152036 Hom.: 8092 Cov.: 32 AF XY: 0.319 AC XY: 23678 AN XY: 74314

African (AFR) AF: 0.266 AC: 11025 AN: 41488

American (AMR) AF: 0.305 AC: 4659 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3468

East Asian (EAS) AF: 0.188 AC: 971 AN: 5160

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4814

European-Finnish (FIN) AF: 0.355 AC: 3753 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24958 AN: 67948

Other (OTH) AF: 0.327 AC: 692 AN: 2116

Alfa AF: 0.343 Hom.: 11498

Bravo AF: 0.319

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.68
PhyloP100		-0.75
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: rs7911506; hg19: chr10-129790840;