rs7895103

Positions:

• chr10-127998694-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254667.8(PTPRE):​c.-8+16398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,082 control chromosomes in the GnomAD database, including 4,534 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 0.24 (4534 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPRE ENST00000254667.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-8+16398T>C		intron_variant		ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.-8+16398T>C		intron_variant		1	NM_006504.6	ENSP00000254667
PTPRE	ENST00000455661.5	c.-1275T>C		5_prime_UTR_variant	1/6	2		ENSP00000416939
PTPRE	ENST00000442830.5	c.-8+16398T>C		intron_variant		5		ENSP00000410540
PTPRE	ENST00000471218.5	c.-8+11299T>C		intron_variant		3		ENSP00000474102

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36747 AN: 151962 Hom.: 4537 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.240

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.242 AC: 36763 AN: 152082 Hom.: 4534 Cov.: 32 AF XY: 0.239 AC XY: 17798 AN XY: 74346

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.241

Alfa AF: 0.252 Hom.: 2728

Bravo AF: 0.243

Asia WGS AF: 0.238 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.053
DANN	Benign	0.70

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: rs7895103; hg19: chr10-129796958;