10-128040939-C-G

Variant names:

• chr10-128040939-C-G
• NM_006504.6:c.58C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006504.6(PTPRE):​c.58C>G​(p.Leu20Val) 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: 32)
• Consequence: PTPRE NM_006504.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.975

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02597636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRE	NM_006504.6	c.58C>G	p.Leu20Val	missense_variant	Exon 3 of 21	ENST00000254667.8	NP_006495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRE	ENST00000254667.8	c.58C>G	p.Leu20Val	missense_variant	Exon 3 of 21	1	NM_006504.6	ENSP00000254667.3
PTPRE	ENST00000455661.5	c.58C>G	p.Leu20Val	missense_variant	Exon 2 of 6	2		ENSP00000416939.1
PTPRE	ENST00000471218.5	c.58C>G	p.Leu20Val	missense_variant	Exon 2 of 6	3		ENSP00000474102.1
PTPRE	ENST00000442830.5	c.58C>G	p.Leu20Val	missense_variant	Exon 4 of 7	5		ENSP00000410540.1

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

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58C>G (p.L20V) alteration is located in exon 3 (coding exon 1) of the PTPRE gene. This alteration results from a C to G substitution at nucleotide position 58, causing the leucine (L) at amino acid position 20 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	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.7
DANN	Benign	0.96
DEOGEN2	Benign	0.085	T;T;T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.026	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.0	L;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.39	N;N;.;N
REVEL	Benign	0.072
Sift	Benign	0.58	T;T;.;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.0050	B;.;.;.
Vest4		0.17
MutPred		0.16		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.12
MPC		0.20
ClinPred		0.035	T
GERP RS		0.31
Varity_R		0.036
gMVP		0.57

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: chr10-129839203;