10-128047408-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PTPRE
NM_006504.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0970
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.073691696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRENM_006504.6 linkc.128C>T p.Ala43Val missense_variant Exon 4 of 21 ENST00000254667.8 NP_006495.1 P23469-1Q96P81

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPREENST00000254667.8 linkc.128C>T p.Ala43Val missense_variant Exon 4 of 21 1 NM_006504.6 ENSP00000254667.3 P23469-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.128C>T (p.A43V) alteration is located in exon 4 (coding exon 2) of the PTPRE gene. This alteration results from a C to T substitution at nucleotide position 128, causing the alanine (A) at amino acid position 43 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
6.9
DANN
Benign
0.91
DEOGEN2
Benign
0.062
T;T;T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.68
T;T;T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.074
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.3
L;.;.;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.080
N;N;.;N
REVEL
Benign
0.084
Sift
Benign
0.27
T;T;.;T
Sift4G
Benign
0.28
T;T;T;T
Polyphen
0.0020
B;.;.;.
Vest4
0.36
MutPred
0.16
Loss of disorder (P = 0.069);Loss of disorder (P = 0.069);Loss of disorder (P = 0.069);Loss of disorder (P = 0.069);
MVP
0.32
MPC
0.20
ClinPred
0.092
T
GERP RS
3.9
Varity_R
0.019
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-129845672; API