chr10-128049562-C-A

Variant names:

• chr10-128049562-C-A
• NM_006504.6:c.316C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006504.6(PTPRE):​c.316C>A​(p.Pro106Thr) variant causes a missense change. 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_006504.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26601267).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	NM_006504.6	MANE Select	c.316C>A	p.Pro106Thr	missense	Exon 6 of 21	NP_006495.1	P23469-1
	PTPRE	NM_001323355.2		c.376C>A	p.Pro126Thr	missense	Exon 5 of 20	NP_001310284.1
	PTPRE	NM_001323356.2		c.370C>A	p.Pro124Thr	missense	Exon 5 of 20	NP_001310285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRE	ENST00000254667.8	TSL:1 MANE Select	c.316C>A	p.Pro106Thr	missense	Exon 6 of 21	ENSP00000254667.3	P23469-1
	PTPRE	ENST00000306042.9	TSL:1	c.142C>A	p.Pro48Thr	missense	Exon 3 of 18	ENSP00000303350.5	P23469-2
	PTPRE	ENST00000870711.1		c.316C>A	p.Pro106Thr	missense	Exon 5 of 20	ENSP00000540770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.088
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.13
Sift	Benign	0.56	T
Sift4G	Uncertain	0.026	D
Polyphen		0.85	P
Vest4		0.70
MutPred		0.24		Gain of phosphorylation at P106 (P = 0.0175)
MVP		0.53
MPC		0.83
ClinPred		0.71	D
GERP RS		3.7
Varity_R		0.095
gMVP		0.63
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr10-129847826;