rs786204928
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP3
The NM_000314.8(PTEN):c.289C>G(p.Gln97Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q97H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.289C>G | p.Gln97Glu | missense_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.808C>G | p.Gln270Glu | missense_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-462C>G | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.289C>G | p.Gln97Glu | missense_variant | 5/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2020 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PTEN-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 97 of the PTEN protein (p.Gln97Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 28, 2022 | The p.Q97E variant (also known as c.289C>G), located in coding exon 5 of the PTEN gene, results from a C to G substitution at nucleotide position 289. The glutamine at codon 97 is replaced by glutamic 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 05;102:943-955). In addition, this variant demonstrated possibly wild type-like intracellular protein abundance on one multiplex functional assay (Matreyek KA et al. Nat Genet, 2018 06;50:874-882). This amino acid position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at