10-87965334-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000314.8(PTEN):āc.1074G>Cā(p.Glu358Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,457,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E358K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.1074G>C | p.Glu358Asp | missense_variant | 9/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.1593G>C | p.Glu531Asp | missense_variant | 10/10 | ||
PTEN | NM_001304718.2 | c.483G>C | p.Glu161Asp | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.1074G>C | p.Glu358Asp | missense_variant | 9/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244502Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132102
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1457580Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2AN XY: 724728
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 17, 2021 | This missense variant replaces glutamic acid with aspartic acid at codon 358 of the PTEN protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/244502 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 22, 2023 | The p.E358D variant (also known as c.1074G>C), located in coding exon 9 of the PTEN gene, results from a G to C substitution at nucleotide position 1074. The glutamic acid at codon 358 is replaced by aspartic acid, an amino acid with highly similar properties. In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was wild type-like (Mighell TL et al. Am J Hum Genet, 2018 May;102:943-955). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
PTEN hamartoma tumor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2022 | This variant has not been reported in the literature in individuals affected with PTEN-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 231962). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 358 of the PTEN protein (p.Glu358Asp). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29706350) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at