NM_006504.6:c.-8+16398T>C

Variant names:

• chr10-127998694-T-C
• rs7895103
• NM_006504.6:c.-8+16398T>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+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 NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 10 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 (SAS) allele frequency at 95% confidence interval = 0.292 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+16398T>C		intron	N/A	NP_006495.1	P23469-1
	PTPRE	NM_001323354.2		c.-1275T>C		5_prime_UTR	Exon 1 of 20	NP_001310283.1	P23469-1
	PTPRE	NM_001323355.2		c.54-42181T>C		intron	N/A	NP_001310284.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.-8+16398T>C		intron	N/A	ENSP00000254667.3	P23469-1
	PTPRE	ENST00000455661.5	TSL:2	c.-1275T>C		5_prime_UTR	Exon 1 of 6	ENSP00000416939.1	Q5VWH5
	PTPRE	ENST00000870711.1		c.-7-42181T>C		intron	N/A	ENSP00000540770.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.225 AC: 9334 AN: 41478

American (AMR) AF: 0.239 AC: 3651 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3468

East Asian (EAS) AF: 0.175 AC: 906 AN: 5178

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4818

European-Finnish (FIN) AF: 0.191 AC: 2016 AN: 10572

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17372 AN: 67990

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.253 Hom.: 3037

Bravo AF: 0.243

Asia WGS AF: 0.238 AC: 831 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	0.053
DANN	Benign	0.70
PhyloP100		-3.0
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: rs7895103; hg19: chr10-129796958;