Genetic Variant NM_006504.6:c.128C>T (chr10-128047408-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006504.6(PTPRE):c.128C>T(p.Ala43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A43T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PTPRE
NM_006504.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970

Publications

0 publications found

Variant links:

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]

PTPRE links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073691696).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRE	NM_006504.6	MANE Select	c.128C>T	p.Ala43Val	missense	Exon 4 of 21	NP_006495.1	P23469-1
PTPRE	NM_001323355.2		c.188C>T	p.Ala63Val	missense	Exon 3 of 20	NP_001310284.1
PTPRE	NM_001323356.2		c.188C>T	p.Ala63Val	missense	Exon 3 of 20	NP_001310285.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.128C>T	p.Ala43Val	missense	Exon 4 of 21	ENSP00000254667.3	P23469-1
PTPRE	ENST00000870711.1		c.128C>T	p.Ala43Val	missense	Exon 3 of 20	ENSP00000540770.1
PTPRE	ENST00000870713.1		c.128C>T	p.Ala43Val	missense	Exon 3 of 20	ENSP00000540772.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.9

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.062

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.68

M_CAP

Benign

0.017

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

PhyloP100

-0.097

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.080

REVEL

Benign

0.084

Sift

Benign

0.27

Sift4G

Benign

0.28

Polyphen

0.0020

Vest4

0.36

MutPred

0.16

Loss of disorder (P = 0.069)

MVP

0.32

MPC

0.20

ClinPred

0.092

GERP RS

3.9

PromoterAI

-0.075

Neutral

(source)

Varity_R

0.019

gMVP

0.55

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over