chr10-127993757-T-C

Variant names:

• chr10-127993757-T-C
• rs7904367
• NM_006504.6:c.-8+11461T>C

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+11461T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 151,876 control chromosomes in the GnomAD database, including 38,676 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 0.71 (38676 hom., cov: 31)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	NM_006504.6	MANE Select	c.-8+11461T>C		intron	N/A	NP_006495.1	P23469-1
	PTPRE	NM_001323355.2		c.54-47118T>C		intron	N/A	NP_001310284.1
	PTPRE	NM_001323356.2		c.54-47118T>C		intron	N/A	NP_001310285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.-8+11461T>C		intron	N/A	ENSP00000254667.3	P23469-1
	PTPRE	ENST00000870711.1		c.-7-47118T>C		intron	N/A	ENSP00000540770.1
	PTPRE	ENST00000870713.1		c.-8+6362T>C		intron	N/A	ENSP00000540772.1

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107340 AN: 151758 Hom.: 38622 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.707 AC: 107447 AN: 151876 Hom.: 38676 Cov.: 31 AF XY: 0.708 AC XY: 52512 AN XY: 74184

African (AFR) AF: 0.856 AC: 35445 AN: 41406

American (AMR) AF: 0.653 AC: 9971 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3148 AN: 5150

South Asian (SAS) AF: 0.659 AC: 3175 AN: 4816

European-Finnish (FIN) AF: 0.691 AC: 7261 AN: 10506

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44078 AN: 67944

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

Alfa AF: 0.655 Hom.: 54463

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.97
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: rs7904367; hg19: chr10-129792021;