10-128049624-C-G

Position:

• chr10-128049624-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323357.2(PTPRE):​c.-192C>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRE NM_001323357.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.801

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

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=0.0984945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.378C>G	p.Ile126Met	missense_variant	6/21	ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.378C>G	p.Ile126Met	missense_variant	6/21	1	NM_006504.6	ENSP00000254667.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.378C>G (p.I126M) alteration is located in exon 6 (coding exon 4) of the PTPRE gene. This alteration results from a C to G substitution at nucleotide position 378, causing the isoleucine (I) at amino acid position 126 to be replaced by a methionine (M). 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	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.6
DANN	Benign	0.44
DEOGEN2	Benign	0.053	T;T;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.50	N;N;N;N
REVEL	Benign	0.026
Sift	Uncertain	0.025	D;T;T;D
Sift4G	Benign	0.28	T;D;D;T
Polyphen		0.082	B;.;.;B
Vest4		0.19
MutPred		0.31		Gain of disorder (P = 0.0985);Gain of disorder (P = 0.0985);Gain of disorder (P = 0.0985);.;
MVP		0.18
MPC		0.21
ClinPred		0.091	T
GERP RS		0.43
Varity_R		0.25
gMVP		0.36

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: chr10-129847888;