rs12049671

Variant names:

• chr10-127939367-C-T
• rs12049671
• NM_006504.6:c.-31+32058C>T

Variant summary

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

The NM_006504.6(PTPRE):​c.-31+32058C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,180 control chromosomes in the GnomAD database, including 1,871 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 0.15 (1871 hom., cov: 32)
• Consequence: PTPRE NM_006504.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 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.-31+32058C>T		intron	N/A	NP_006495.1	P23469-1
	PTPRE	NM_001323355.2		c.53+32058C>T		intron	N/A	NP_001310284.1
	PTPRE	NM_001323356.2		c.53+32058C>T		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.-31+32058C>T		intron	N/A	ENSP00000254667.3	P23469-1
	PTPRE	ENST00000870711.1		c.-8+32058C>T		intron	N/A	ENSP00000540770.1
	PTPRE	ENST00000968589.1		c.-31+8234C>T		intron	N/A	ENSP00000638648.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22774 AN: 152060 Hom.: 1868 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.150 AC: 22792 AN: 152180 Hom.: 1871 Cov.: 32 AF XY: 0.152 AC XY: 11303 AN XY: 74396

African (AFR) AF: 0.100 AC: 4170 AN: 41524

American (AMR) AF: 0.209 AC: 3203 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5164

South Asian (SAS) AF: 0.206 AC: 994 AN: 4832

European-Finnish (FIN) AF: 0.143 AC: 1512 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10568 AN: 67988

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.149 Hom.: 1081

Bravo AF: 0.155

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		0.097
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: rs12049671; hg19: chr10-129737631;