10-128047402-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.122C>T​(p.Pro41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PTPRE
NM_006504.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783
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=0.128835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRENM_006504.6 linkc.122C>T p.Pro41Leu 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.122C>T p.Pro41Leu missense_variant Exon 4 of 21 1 NM_006504.6 ENSP00000254667.3 P23469-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000807
AC:
2
AN:
247984
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134700
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460532
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726604
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.122C>T (p.P41L) 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 122, causing the proline (P) at amino acid position 41 to be replaced by a leucine (L). 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
0.083
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
18
DANN
Benign
0.92
DEOGEN2
Benign
0.095
T;T;T;.
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.75
T;T;T;T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.13
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.5
L;.;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.5
N;D;.;D
REVEL
Benign
0.054
Sift
Benign
0.031
D;T;.;T
Sift4G
Benign
0.27
T;T;T;T
Polyphen
0.012
B;.;.;.
Vest4
0.42
MutPred
0.28
Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);
MVP
0.48
MPC
0.21
ClinPred
0.14
T
GERP RS
2.9
Varity_R
0.037
gMVP
0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751352191; hg19: chr10-129845666; API