Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_000314.8 | MANE Select | 8515 nt | 846–2057 |
| NM_000314.7 | RefSeq Select | 8514 nt | 845–2056 |
| NM_000314.5 | Alternative | 8719 nt | 1032–2243 |
| NM_000314.4 | Alternative | 5572 nt | 1032–2243 |
| NM_000314.3 | Alternative | 3416 nt | 1032–2243 |
| NM_000314.6 | Alternative | 8718 nt | 1032–2243 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open"This variant has been reported in ClinVar as Uncertain significance (1 clinical laboratories) and as Benign (1 clinical laboratories)."
COSMIC Somatic Evidence
OpenFunctional Impact & Domains
Functional Domain
The PTEN *8t>G variant has not been functionally characterized, and its biological significance remains unknown.
Click on previews to view full database entries. External databases may require institutional access.
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -14 bp |
| Donor Loss (DL) | 0.0 | -14 bp |
| Acceptor Gain (AG) | 0.0 | -193 bp |
| Donor Gain (DG) | 0.0 | -327 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to VCEP guidelines, the PVS1 rule is: "Null Variant (nonsense, fs, start codon, splicing +1/2, startgain, single or multi-exon deletion) in a gene where LOF is a known mechanism of disease". The evidence for this variant shows it is NM_000314.8:c.*8T>G located in the 3′ UTR, not predicted to truncate or abolish the protein. Therefore, this criterion is not applied because the variant does not create a null allele.
PS1 (Not Applied)
According to VCEP guidelines, the PS1 rule is: "Same amino acid change as a previously established pathogenic variant regardless of nucleotide change OR different variant at same nucleotide position as a pathogenic splicing variant...". The evidence for this variant shows no amino acid change (3′ UTR). Therefore, this criterion is not applied because there is no amino acid alteration.
PS2 (Not Applied)
According to VCEP guidelines, the PS2 rule is: "De novo (both maternity and paternity confirmed) in a patient with the disease and no family history". There are no reports of de novo occurrence. Therefore, this criterion is not applied due to lack of de novo evidence.
PS3 (Not Applied)
According to PTEN Pre-processing findings, functional studies for this variant have not been characterized ("The PTEN *8T>G variant has not been functionally characterized"). Therefore, PS3 is not applied due to absence of functional assay data.
PS4 (Not Applied)
According to VCEP guidelines, the PS4 rule is: "The prevalence of the variant in affected individuals is significantly increased compared with controls or specificity score ≥4". No case/control or proband data are available. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to VCEP guidelines, the PM1 rule is: "Located in a mutational hot spot and/or critical functional domain (residues 90–94, 123–130, 166–168)". The variant is in the 3′ UTR and not within any catalytic motif. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the PM2 rule is: "Absent in population databases present at <0.00001 allele frequency in gnomAD". The evidence shows the variant is not found in gnomAD or other large population databases. Therefore, PM2 is applied at Supporting strength.
PM3 (Not Applied)
According to standard ACMG, the PM3 rule applies to recessive cases with observed in trans pathogenic variants. This variant is in a dominant LOF gene and there is no evidence of compound heterozygosity. Therefore, PM3 is not applied.
PM4 (Not Applied)
According to VCEP guidelines, the PM4 rule is: "Protein length changes due to in-frame deletions/insertions or stop-loss variants in functional regions". This is a single-nucleotide change in the 3′ UTR. Therefore, PM4 is not applied.
PM5 (Not Applied)
According to VCEP guidelines, the PM5 rule is: "Missense change at a residue where a different missense change is pathogenic". This variant does not alter an amino acid. Therefore, PM5 is not applied.
PM6 (Not Applied)
According to VCEP guidelines, the PM6 rule is: "Assumed de novo occurrence without confirmation". No de novo data are available. Therefore, PM6 is not applied.
PP1 (Not Applied)
According to VCEP guidelines, the PP1 rule is: "Co-segregation with disease in multiple affected family members". No segregation data are reported. Therefore, PP1 is not applied.
PP2 (Not Applied)
According to standard ACMG, the PP2 rule is: "Missense variant in a gene with low rate of benign missense variation where missense is common mechanism". This variant is noncoding. Therefore, PP2 is not applied.
PP3 (Not Applied)
According to VCEP guidelines, the PP3 rule is: "Multiple lines of computational evidence support a deleterious effect". In silico tools (CADD 2.04, SpliceAI = 0) predict no impact. Therefore, PP3 is not applied.
PP4 (Not Applied)
According to standard ACMG, the PP4 rule is: "Patient’s phenotype is highly specific for a single gene disorder". No phenotype data are provided. Therefore, PP4 is not applied.
PP5 (Not Applied)
According to standard ACMG, the PP5 rule is: "Reputable source without evidence reports variant as pathogenic". ClinVar entries are conflicting (VUS and benign). Therefore, PP5 is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the BA1 rule is: "gnomAD allele frequency >0.00056". The variant is absent. Therefore, BA1 is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the BS1 rule is: "gnomAD allele frequency 0.000043–0.00056". The variant is absent. Therefore, BS1 is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the BS2 rule is: "Observed as homozygous in healthy individuals". No such observations exist. Therefore, BS2 is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the BS3 rule is: "Well-established functional studies show no damaging effect". No splicing or functional assays have been performed. Therefore, BS3 is not applied.
BS4 (Not Applied)
According to VCEP guidelines, the BS4 rule is: "Lack of segregation in affected members of ≥2 families". No segregation data are available. Therefore, BS4 is not applied.
BP1 (Not Applied)
According to standard ACMG, the BP1 rule is: "Missense in a gene where only truncating variants cause disease". This is noncoding. Therefore, BP1 is not applied.
BP2 (Not Applied)
According to VCEP guidelines, the BP2 rule is: "Observed in trans with a pathogenic PTEN variant". No such observations exist. Therefore, BP2 is not applied.
BP3 (Not Applied)
According to standard ACMG, the BP3 rule is: "In-frame indels in a repetitive region". This is a SNV in the 3′ UTR. Therefore, BP3 is not applied.
BP4 (Supporting)
According to VCEP guidelines, the BP4 rule is: "Multiple lines of computational evidence suggest no impact on gene or gene product". In silico tools (SpliceAI = 0, CADD = 2.04) predict benign. Therefore, BP4 is applied at Supporting strength.
BP5 (Not Applied)
According to VCEP guidelines, the BP5 rule is: "Variant found in a case with an alternate molecular basis for disease". No such case data exist. Therefore, BP5 is not applied.
BP6 (Not Applied)
According to standard ACMG, the BP6 rule is: "Reputable source without evidence reports variant as benign". ClinVar entries are conflicting. Therefore, BP6 is not applied.
BP7 (Not Applied)
According to VCEP guidelines, the BP7 rule is: "A synonymous or intronic variant at or beyond +7/-21 with no splicing impact". This is a 3′ UTR variant. Therefore, BP7 is not applied.