NM_006504.6:c.-7-19579C>G

Variant names:

• chr10-128021296-C-G
• rs10764734
• NM_006504.6:c.-7-19579C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006504.6(PTPRE):​c.-7-19579C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,982 control chromosomes in the GnomAD database, including 13,926 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 0.43 (13926 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 1 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 = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.-7-19579C>G		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.-7-19579C>G		intron_variant	Intron 2 of 20	1	NM_006504.6	ENSP00000254667.3
PTPRE	ENST00000455661.5	c.-7-19579C>G		intron_variant	Intron 1 of 5	2		ENSP00000416939.1
PTPRE	ENST00000471218.5	c.-7-19579C>G		intron_variant	Intron 1 of 5	3		ENSP00000474102.1
PTPRE	ENST00000442830.5	c.-7-19579C>G		intron_variant	Intron 3 of 6	5		ENSP00000410540.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64585 AN: 151864 Hom.: 13928 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.425 AC: 64593 AN: 151982 Hom.: 13926 Cov.: 32 AF XY: 0.421 AC XY: 31254 AN XY: 74320

African (AFR) AF: 0.406 AC: 16798 AN: 41420

American (AMR) AF: 0.306 AC: 4675 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3466

East Asian (EAS) AF: 0.425 AC: 2199 AN: 5172

South Asian (SAS) AF: 0.404 AC: 1950 AN: 4828

European-Finnish (FIN) AF: 0.441 AC: 4660 AN: 10576

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31170 AN: 67936

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.446 Hom.: 1891

Bravo AF: 0.413

Asia WGS AF: 0.368 AC: 1281 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	2.0
DANN	Benign	0.65
PhyloP100		-0.13
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: rs10764734; hg19: chr10-129819560;