PTEN c.80-27_80-11delinsT, p.?
NM_000314.8:c.80-27_80-11delinsT
Variant of Uncertain Significance (VUS)
The variant NM_000314.8:c.80-27_80-11delinsT in PTEN remains classified as VUS. Only PM2_Supporting (absent from population databases) is met, with no additional evidence to support pathogenicity or benign impact.
ACMG/AMP Criteria Applied
PM2
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.80-27_80-11delinsT
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
Genome Browser
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HGVS InputNM_000314:c.80-27_80-11delinsT
Active Tracks
ConservationRefSeqClinVargnomAD
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Clinical Data
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.05%
0.1%
1%
5%
10%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications (0)
No publication details.
Clinical Statement
Functional Impact
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
Computational Analysis
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific) VCEP Guidelines
PVS1
PVS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PVS1 is: "**Very Strong Strength**: Very Strong Use PTEN PVS1 decision tree. Modification Type: Disease-specific." The evidence for this variant shows: transcript and variant consequence are unknown and no canonical ±1/2 splice site change is described. Therefore, this criterion is not applied because required transcript information and demonstration of loss-of-function impact are missing.
PS1
PS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PS1 is: "**Strong Strength**: Strong 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, where in silico models predict impact equal to or greater than the known pathogenic variant." The evidence for this variant shows: no protein change is known and no previously established pathogenic variant at the same residue. Therefore, this criterion is not applied because the amino acid change is unknown and there is no matching pathogenic comparison.
PS2
PS2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PS2 is: "**Strong Strength**: Strong De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history." The evidence for this variant shows: no de novo occurrence data are available. Therefore, this criterion is not applied due to absence of de novo evidence.
PS3
PS3 (Not Applied) Strength Modified
According to PTEN Pre-processing guidelines, the finding for PS3 is: "Functional studies (PS3): The PTEN 80-27_80-11delinst variant has not been functionally characterized." The evidence for this variant shows: no in vitro or in vivo functional data exist. Therefore, this criterion is not applied because functional impact has not been assessed.
PS4
PS4 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PS4 is: "The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls (or proband counts reaching defined specificity scores)." The evidence for this variant shows: no case–control or proband data are available. Therefore, this criterion is not applied due to lack of association data.
PM1
PM1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM1 is: "**Moderate Strength**: Moderate Located in a mutational hot spot and/or critical and well-established functional domain (residues in catalytic motifs: 90-94, 123-130, 166-168)." The evidence for this variant shows: this is an intronic change outside defined catalytic motifs. Therefore, this criterion is not applied because the variant is not in a hotspot or critical domain.
PM2
PM2 (Supporting) Strength Modified
According to VCEP guidelines, the rule for PM2 is: "**Supporting Strength**: Supporting Absent in population Databases present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population. If multiple alleles are present within any subpopulation, allele frequency in that subpopulation must be <0.00002 (0.002%). Modification Type: Disease-specific." The evidence for this variant shows: absent from gnomAD and other population databases. Therefore, this criterion is applied at Supporting strength because the variant is not observed in population controls.
PM3
PM3 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PM3 is: "For recessive disorders, detected in trans with a pathogenic variant." The evidence for this variant shows: no data on allelic phase or recessive inheritance. Therefore, this criterion is not applied due to lack of trans observation.
PM4
PM4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM4 is: "**Moderate Strength**: Moderate Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants (and impacting at least one residue in a catalytic motif)." The evidence for this variant shows: this is an intronic delins with no defined in-frame coding change. Therefore, this criterion is not applied because there is no protein length alteration.
PM5
PM5 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM5 is: "**Moderate Strength**: Moderate Missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before (with appropriate BLOSUM62 score)." The evidence for this variant shows: no missense amino acid change is described. Therefore, this criterion is not applied due to absence of a missense alteration.
PM6
PM6 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PM6 is: "**Strong Strength**: Strong Two probands with presumed de novo occurrence..." The evidence for this variant shows: no presumed de novo observations. Therefore, this criterion is not applied.
PP1
PP1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PP1 is: "**Supporting Strength**: Supporting Co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed." The evidence for this variant shows: no family segregation data. Therefore, this criterion is not applied.
PP2
PP2 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP2 is: "Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease." The evidence for this variant shows: not a missense change. Therefore, this criterion is not applied.
PP3
PP3 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for PP3 is: "**Supporting Strength**: Supporting Multiple lines of computational evidence support a deleterious effect (Splicing variants: concordance of SpliceAI and VarSeak)." The evidence for this variant shows: SpliceAI score 0.37 indicates limited impact and no concordant computational evidence. Therefore, this criterion is not applied.
PP4
PP4 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP4 is: "Phenotype or family history highly specific for a disease with a single genetic etiology." The evidence for this variant shows: no phenotype data provided. Therefore, this criterion is not applied.
PP5
PP5 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for PP5 is: "Reputable source reports variant as pathogenic." The evidence for this variant shows: not found in ClinVar or other databases. Therefore, this criterion is not applied.
BA1
BA1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BA1 is: "**Stand Alone Strength**: Stand Alone gnomAD Filtering allele frequency >0.00056 (0.056%)." The evidence for this variant shows: absent from population databases. Therefore, this criterion is not applied.
BS1
BS1 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS1 is: "**Strong Strength**: Strong gnomAD Filtering allele frequency from 0.000043 up to 0.00056." The evidence for this variant shows: absent from gnomAD. Therefore, this criterion is not applied.
BS2
BS2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS2 is: "**Strong Strength**: Strong Observed in the homozygous state in a healthy or PHTS-unaffected individual (one observation if confirmed)." The evidence for this variant shows: no homozygous observations. Therefore, this criterion is not applied.
BS3
BS3 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS3 is: "**Strong Strength**: Strong Well-established in vitro or in vivo functional studies shows no damaging effect on protein function (including splicing assays for intronic variants)." The evidence for this variant shows: no functional splicing studies. Therefore, this criterion is not applied.
BS4
BS4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BS4 is: "**Strong Strength**: Strong Lack of segregation in affected members of two or more families." The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
BP1
BP1 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for BP1 is: "Missense variant in a gene for which primarily truncating variants are known to cause disease." The evidence for this variant shows: not a missense variant. Therefore, this criterion is not applied.
BP2
BP2 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP2 is: "**Supporting Strength**: Supporting Observed in trans with a pathogenic or likely pathogenic PTEN variant OR at least three observations in cis with different pathogenic PTEN variants." The evidence for this variant shows: no cis/trans phase data. Therefore, this criterion is not applied.
BP3
BP3 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for BP3 is: "In-frame deletions/insertions in a repetitive region without a known function." The evidence for this variant shows: intronic region not within defined repeat. Therefore, this criterion is not applied.
BP4
BP4 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP4 is: "**Supporting Strength**: Supporting Multiple lines of computational evidence suggest no impact on gene or gene product (Splicing variants: concordance of SpliceAI and VarSeak)." The evidence for this variant shows: SpliceAI score 0.37 alone is inconclusive and no concordance. Therefore, this criterion is not applied.
BP5
BP5 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP5 is: "**Supporting Strength**: Supporting Variant found in a case with an alternate molecular basis for disease." The evidence for this variant shows: no alternate molecular basis reported. Therefore, this criterion is not applied.
BP6
BP6 (Not Applied) Strength Modified
According to standard ACMG guidelines, the rule for BP6 is: "Reputable source reports variant as benign." The evidence for this variant shows: no database entry. Therefore, this criterion is not applied.
BP7
BP7 (Not Applied) Strength Modified
According to VCEP guidelines, the rule for BP7 is: "**Supporting Strength**: Supporting A synonymous or intronic variant at or beyond +7/-21 for which splicing prediction algorithms predict no impact." The evidence for this variant shows: spans positions -27 to -11 and computational predictions are inconclusive. Therefore, this criterion is not applied.