rs1554900515
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PP2PP3_StrongPP5_Moderate
The ENST00000371953.8(PTEN):c.497T>A(p.Val166Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V166I) has been classified as Likely benign.
Frequency
Consequence
ENST00000371953.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.497T>A | p.Val166Glu | missense_variant | 6/9 | ENST00000371953.8 | NP_000305.3 | |
PTEN | NM_001304717.5 | c.1016T>A | p.Val339Glu | missense_variant | 7/10 | NP_001291646.4 | ||
PTEN | NM_001304718.2 | c.-95T>A | 5_prime_UTR_variant | 6/9 | NP_001291647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.497T>A | p.Val166Glu | missense_variant | 6/9 | 1 | NM_000314.8 | ENSP00000361021 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2017 | The p.V166E variant (also known as c.497T>A), located in coding exon 6 of the PTEN gene, results from a T to A substitution at nucleotide position 497. The valine at codon 166 is replaced by glutamic acid, an amino acid with dissimilar properties. This variant has been determined to be the result of a de novo mutation in one family within our clinical cohort (Ambry internal data). Based on internal structural analysis, this alteration was determined to be structurally deleterious because the variant is more destabilizing than known pathogenic variants nearby (Lee JO et al. Cell, 1999 Oct;99:323-34). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at