PTEN c.-533_-532delinsTT, p.?
NM_000314.8:c.-533_-532delinsTT
Population Frequency
0.0 in 100,000
Rare
ClinVar Classification
Unknown
0 publications
REVEL Score
N/A
Not Available
COSMIC Recurrence
0 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
PTEN
Transcript
NM_000314.8
MANE Select
Total Exons
9
Strand
Forward (+)
Reference Sequence
NC_000010.10
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_000314.7 | RefSeq Select | 9 exons | Forward |
| NM_000314.5 | Alternative | 9 exons | Forward |
| NM_000314.4 | Alternative | 9 exons | Forward |
| NM_000314.3 | Alternative | 9 exons | Forward |
| NM_000314.6 | Alternative | 9 exons | Forward |
Variant Details
HGVS Notation
NM_000314.8:c.-533_-532delinsTT
Protein Change
?
Location
Exon 1
(Exon 1 of 9)
5'
Exon Structure (9 total)
3'
Functional Consequence
Loss of Function
Related Variants
Variant interpretation based on transcript NM_000314.8
Clinical Evidence
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications
0 publications
Clinical Statement
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Functional Studies
Summary
The PTEN -533_-532delinsTT variant has not been functionally characterized, and its biological significance remains unknown.
Computational Evidence
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria
VCEP Guidelines
PVS1
PVS1 (Not Applied)
Strength Modified
According to VCEP PTEN PVS1 decision tree guidelines, PVS1 applies only to null variants (nonsense, frameshift, canonical ±1/2 splice sites, initiation codon, single/multi‐exon deletions) in a gene where loss of function is a known mechanism. The variant NM_000314.8:c.-533_-532delinsTT is in the 5′UTR/promoter region and does not create a null allele. Therefore, PVS1 is not applied.
PS1
PS1 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, PS1 requires the same amino acid change as a known pathogenic variant. This variant is non-coding with no amino acid change. Therefore, PS1 is not applied.
PS2
PS2 (Not Applied)
Strength Modified
According to VCEP guidelines, PS2 requires confirmed de novo occurrence with maternity and paternity. No de novo data are available for this variant. Therefore, PS2 is not applied.
PS3
PS3 (Not Applied)
Strength Modified
According to PTEN pre-processing, 'The PTEN -533_-532delinsTT variant has not been functionally characterized, and its biological significance remains unknown.' The evidence shows no functional study data. Therefore, PS3 is not applied.
PS4
PS4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PS4 requires a statistically significant increase in variant prevalence in affected individuals or multiple probands with disease specificity. No case-control or proband data are available. Therefore, PS4 is not applied.
PM1
PM1 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, PM1 applies to variants located in mutational hot spots or critical functional domains (residues 90–94, 123–130, 166–168). This variant lies in the 5′UTR outside these domains. Therefore, PM1 is not applied.
PM2
PM2 (Supporting)
Strength Modified
According to VCEP guidelines, PM2: 'Supporting – Absent in population databases; present at <0.00001 allele frequency in gnomAD.' The variant is not found in gnomAD or other large databases (MAF=0%). Therefore, PM2 is applied at Supporting strength.
PM3
PM3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PM3 applies to detected variants in trans with a pathogenic variant for recessive disorders. PTEN-associated conditions are dominantly inherited, and no trans data exist. Therefore, PM3 is not applied.
PM4
PM4 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, PM4 applies to in-frame indels in non-repeat regions causing protein length changes in catalytic motifs. This is a noncoding variant; no protein length change. Therefore, PM4 is not applied.
PM5
PM5 (Not Applied)
Strength Modified
According to VCEP guidelines, PM5 applies to missense changes at residues with other pathogenic missense variants. This variant is noncoding. Therefore, PM5 is not applied.
PM6
PM6 (Not Applied)
Strength Modified
According to VCEP guidelines, PM6 applies to assumed de novo cases without paternity/maternity confirmation. No de novo data exist. Therefore, PM6 is not applied.
PP1
PP1 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, PP1 requires co-segregation in multiple affected family members. No segregation data are available. Therefore, PP1 is not applied.
PP2
PP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP2 applies to missense variants in genes with low benign missense variation and common missense mechanism. This variant is noncoding. Therefore, PP2 is not applied.
PP3
PP3 (Not Applied)
Strength Modified
According to VCEP guidelines, PP3 requires multiple lines of computational evidence supporting a deleterious effect. Computational predictions (SpliceAI max score 0) show no predicted impact. Therefore, PP3 is not applied.
PP4
PP4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP4 applies to highly specific phenotypes with single genetic etiology. No phenotype data are provided. Therefore, PP4 is not applied.
PP5
PP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP5 applies to variants reported as pathogenic by reputable sources. The variant is not in ClinVar or other databases. Therefore, PP5 is not applied.
BA1
BA1 (Not Applied)
Strength Modified
According to VCEP guidelines, BA1 applies to variants with gnomAD allele frequency >0.00056. The variant is absent. Therefore, BA1 is not applied.
BS1
BS1 (Not Applied)
Strength Modified
According to VCEP guidelines, BS1 applies to allele frequency 0.000043–0.00056. The variant is absent. Therefore, BS1 is not applied.
BS2
BS2 (Not Applied)
Strength Modified
According to VCEP guidelines, BS2 requires observation in homozygous state in healthy individuals. No such observations exist. Therefore, BS2 is not applied.
BS3
BS3 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, BS3 requires functional assays showing no damaging effect. No assays exist. Therefore, BS3 is not applied.
BS4
BS4 (Not Applied)
Strength Modified
According to VCEP guidelines, BS4 requires lack of segregation in ≥2 families. No segregation data. Therefore, BS4 is not applied.
BP1
BP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP1 applies to missense variants in genes where only truncating variants cause disease. This variant is noncoding. Therefore, BP1 is not applied.
BP2
BP2 (Not Applied)
Strength Modified
According to VCEP guidelines, BP2 applies to variants observed in trans with pathogenic variants for dominant conditions or multiple cis observations. No such data exist. Therefore, BP2 is not applied.
BP3
BP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP3 applies to in-frame indels in repetitive regions. This variant is not in a repetitive region and is noncoding. Therefore, BP3 is not applied.
BP4
BP4 (Supporting)
According to VCEP guidelines, BP4: 'Supporting – Multiple lines of computational evidence suggest no impact on gene or gene product. Splicing variants: Concordance of SpliceAI and VarSeak.' SpliceAI predicts no impact (score 0) and no deleterious in silico predictions exist. Therefore, BP4 is applied at Supporting strength.
BP5
BP5 (Not Applied)
Strength Modified
According to VCEP PTEN guidelines, BP5 applies when an alternate molecular basis for disease is present. No alternate diagnosis data. Therefore, BP5 is not applied.
BP6
BP6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP6 applies to reports from reputable sources without evidence. No such reports exist. Therefore, BP6 is not applied.
BP7
BP7 (Not Applied)
Strength Modified
According to VCEP guidelines, BP7 applies to synonymous or intronic variants at or beyond +7/−21 with no splice impact. This is a 5′UTR exonic variant, not an intronic variant. Therefore, BP7 is not applied.