10-127993757-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-8+11461T>C		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+11461T>C		intron_variant	Intron 2 of 20	1	NM_006504.6	ENSP00000254667.3
PTPRE	ENST00000471218.5	c.-8+6362T>C		intron_variant	Intron 1 of 5	3		ENSP00000474102.1
PTPRE	ENST00000442830.5	c.-8+11461T>C		intron_variant	Intron 3 of 6	5		ENSP00000410540.1

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

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.650

Alfa AF: 0.647 Hom.: 41760

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.59

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: rs7904367; hg19: chr10-129792021;