About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.348del, p.(Asp116GlufsTer18)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen PTEN VCEP v3.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PVS1Very strong
PVS1 · very strong
NM_000314.8:c.348del is a frameshift variant predicted to cause p.(Asp116GlufsTer18). The PTEN-specific PVS1 decision tree assigns PVS1 to frameshift variants in biologically relevant transcript NM_000314.8 when the stop/disruption is at or 5' to p.D375 (c.1121); p.Asp116fs is well upstream of this threshold and is predicted to undergo NMD.
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 and gnomAD v4.1. Under the PTEN specification, PM2 is applied at Supporting strength when allele frequency is <0.00001 (0.001%) and, if multiple alleles are present in a subpopulation, the subpopulation frequency is <0.00002 (0.002%); absence from both datasets satisfies this rule.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Generic ACMG/AMP 2015 combination rules fallback was used because no explicit PTEN VCEP-specific final classification framework was retrieved in the workspace. Under the retrieved generic_acmg_combination_rules, the applied evidence set is PVS1 plus PM2_Supporting, which does not meet a defined Pathogenic or Likely Pathogenic combination.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PTEN VCEP v3.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 4 not met · 7 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000314.8:c.348del predicts PTEN p.(Asp116GlufsTer18), a frameshift expected to truncate the protein early in exon 5.
The PTEN PVS1 decision tree assigns PVS1 to frameshift variants in NM_000314.8 when the stop/disruption occurs at or 5' to p.D375 (c.1121); this variant truncates at p.Asp116fs, which is well upstream of that threshold and is consistent with loss of function.
The variant is absent from gnomAD v2.1 and gnomAD v4.1, and the PTEN specification applies PM2 at Supporting strength for variants with allele frequency below 0.00001, with a subpopulation threshold below 0.00002 when multiple alleles are present.
No PTEN-specific final classification framework was retrieved, so the generic ACMG/AMP combination rules were used as fallback; with PVS1 and PM2_Supporting alone, this evidence set does not reach a defined pathogenic or likely pathogenic combination under those rules, and the variant is therefore classified as a variant of uncertain significance pending human review.
No criteria match.
Met · 2
PVS1 Very strongNM_000314.8:c.348del is a frameshift variant predicted to cause p.(Asp116GlufsTer18). The PTEN-specific PVS1 decision tree assigns PVS1 to frameshift variants in biologically relevant transcript NM_000314.8 when the stop/disruption is at or 5' to p.D375 (c.1121); p.Asp116fs is well upstream of this threshold and is predicted to undergo NMD. Details ▾Hide ▴
Rule
Use PTEN PVS1 decision tree; frameshift variants with stop/disruption at or 5' to p.D375 (c.1121) in NM_000314.8 are assigned PVS1.
Evidence considered
- NM_000314.8:c.348del
- NP_000305.3:p.(Asp116GlufsTer18)
- PTEN PVS1 decision tree threshold p.D375 (c.1121)
- variant lies in exon 5
Sources
vcep_p_v_s_1___d_e_c_i_s_i_o_n_t_r_e_e___p_t_e_ncspec ↗
PM2 SupportingThe variant is absent from gnomAD v2.1 and gnomAD v4.1. Under the PTEN specification, PM2 is applied at Supporting strength when allele frequency is <0.00001 (0.001%) and, if multiple alleles are present in a subpopulation, the subpopulation frequency is <0.00002 (0.002%); absence from both datasets satisfies this rule. Details ▾Hide ▴
Rule
PTEN applies PM2 at Supporting strength for variants absent or below the specified gnomAD frequency thresholds.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- PTEN PM2_Supporting threshold <0.00001; subpopulation threshold <0.00002 if multiple alleles present
Sources
Not met · 4 · evaluated, threshold not reached
PM1 The PTEN PM1 specification is limited to catalytic motif residues 90-94, 123-130, and 166-168. This variant affects codon 116, which is outside those defined PM1 residues, and no statistically significant hotspot evidence was provided. Details ▾Hide ▴
Rule
Located in a mutational hot spot and/or critical functional domain; PTEN defines catalytic motifs at residues 90-94, 123-130, and 166-168.
Evidence considered
- protein consequence p.(Asp116GlufsTer18)
- PTEN PM1 motif ranges 90-94, 123-130, 166-168
Sources
BA1 The variant is absent from gnomAD v2.1 and v4.1, so it does not exceed the PTEN BA1 filtering allele frequency threshold of >0.00056 (0.056%). Details ▾Hide ▴
Rule
gnomAD filtering allele frequency >0.00056 (0.056%).
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BA1 threshold >0.00056
Sources
BS1 The variant is absent from gnomAD v2.1 and v4.1, so it does not fall within the PTEN BS1 frequency ranges of 0.000043-0.00056 for Strong or 0.0000043-0.000043 for Supporting evidence. Details ▾Hide ▴
Rule
PTEN BS1 uses specified gnomAD filtering allele frequency ranges for Strong and Supporting evidence.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- BS1 thresholds 0.000043-0.00056 and 0.0000043-0.000043
Sources
BS2 No observation of this variant in the homozygous state in a healthy or PTEN-hamartoma-tumor-syndrome-unaffected individual was provided. Details ▾Hide ▴
Not assessed · 7 · no assessment recorded
PS2 No de novo case data with confirmed maternity and paternity were provided. Details ▾Hide ▴
Rule
De novo occurrence with confirmed maternity and paternity in an affected individual with no family history.
Still missing
- Documented confirmed de novo occurrence in an affected individual with no family history
Sources
PS4 No germline proband counts or PTEN phenotype specificity scoring data were provided to compare case prevalence with controls under the PTEN specification. Details ▾Hide ▴
Rule
Apply by PTEN phenotype specificity score or significant enrichment in affected individuals versus controls.
Still missing
- Proband-level phenotype specificity score or case-control enrichment data
Sources
PM6 No assumed de novo observations in affected individuals without family history were provided. Details ▾Hide ▴
Rule
Apply using PTEN de novo scoring thresholds when maternity/paternity are not fully confirmed.
Still missing
- Assumed or proven de novo case data meeting PTEN PM6 thresholds
Sources
PP1 No segregation data were provided to count informative meioses. Details ▾Hide ▴
Rule
Co-segregation with disease in multiple affected family members, scaled by meioses.
Still missing
- Family segregation data with informative meioses
Sources
BS4 No family data demonstrating lack of segregation were provided. Details ▾Hide ▴
Rule
Lack of segregation in affected members of one family (Supporting) or two or more families (Strong).
Still missing
- Family-level nonsegregation data in one or more affected families
Sources
BP2 No phase data were provided showing this variant in trans with a pathogenic PTEN variant or in cis/phase unknown on at least three occasions with different pathogenic PTEN variants. Details ▾Hide ▴
Rule
Observed in trans with a pathogenic/likely pathogenic PTEN variant, or at least three cis/phase-unknown observations with different pathogenic/likely pathogenic PTEN variants.
Still missing
- Phase data with pathogenic or likely pathogenic PTEN variants
Sources
BP5 No evidence was provided for at least two cases with an alternate highly penetrant molecular diagnosis and a nonoverlapping phenotype. Details ▾Hide ▴
Rule
Variant found in a case with an alternate molecular basis for disease meeting PTEN-specific restrictions.
Still missing
- At least two qualifying alternate molecular diagnoses with nonoverlapping phenotype
Sources
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 is specified for the same amino acid substitution as a known pathogenic variant or equivalent splicing effect. This variant is a frameshift, not a single amino acid substitution. Details ▾Hide ▴
Rule
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change, or equivalent splicing effect at same nucleotide.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
PS3 N/ANo RNA or splicing assay evidence was provided for this deletion, and the PTEN functional dataset indexed for PS3/BS3 is a missense phosphatase assay that does not apply to this frameshift variant. Details ▾Hide ▴
Rule
PS3 applies to RNA/minigene/splicing assays showing splice impact, or to PTEN missense phosphatase assay thresholds from Mighell et al. 2018.
Evidence considered
- mmc2.xlsx applies to missense variants
- no RNA/minigene assay in workspace
Sources
PM3 N/APM3 is not applicable for the PTEN VCEP. Details ▾Hide ▴
PM4 N/APM4 is specified for in-frame insertions/deletions affecting defined motifs or for stop-loss variants. This variant is a frameshift loss-of-function variant, so PM4 does not apply. Details ▾Hide ▴
Rule
Protein length changes due to in-frame insertions/deletions in a non-repeat region or stop-loss variants.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
PM5 N/APM5 is a missense criterion and does not apply to this frameshift variant. Details ▾Hide ▴
Rule
Missense change at a residue where a different pathogenic missense change has been seen before.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
PP2 N/APP2 is a missense criterion and does not apply to this frameshift variant. Details ▾Hide ▴
Rule
Missense variant in a gene with low benign missense variation and where missense is a common disease mechanism.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
PP3 N/APTEN PP3 is specified for missense variants using REVEL or for splicing variants with concordant splice predictors. This exonic frameshift deletion is not a missense variant, is not a splice-region variant, and no concordant splicing framework beyond SpliceAI was provided. Details ▾Hide ▴
Rule
PTEN PP3 applies to missense variants with REVEL >0.7 or splicing variants with concordant splice prediction evidence.
Evidence considered
- max SpliceAI delta score 0.00
- variant is exonic frameshift
Sources
PP4 N/APP4 is not applicable for the PTEN VCEP because phenotype specificity has been incorporated into PS4. Details ▾Hide ▴
BS3 N/ANo functional study showing no damaging effect was provided for this frameshift variant, and the indexed PTEN functional assay file is a missense phosphatase dataset that does not apply here. Details ▾Hide ▴
Rule
BS3 applies to functional studies showing no damaging effect, including missense phosphatase activity >0 in the indexed PTEN assay.
Evidence considered
- mmc2.xlsx applies to missense variants
- no benign functional assay for this deletion
Sources
BP1 N/ABP1 is not applicable for the PTEN VCEP. Details ▾Hide ▴
BP3 N/ABP3 is not applicable for the PTEN VCEP. Details ▾Hide ▴
BP4 N/APTEN BP4 is specified for synonymous or intronic variants with benign splicing predictions, or missense variants with REVEL <0.5. This variant is an exonic frameshift deletion, so BP4 does not apply. Details ▾Hide ▴
Rule
PTEN BP4 applies to synonymous/intronic variants with benign splice predictions or missense variants with REVEL <0.5.
Evidence considered
- max SpliceAI delta score 0.00
- variant is exonic frameshift
Sources
BP6 N/ABP6 is not for use in this VCEP. Details ▾Hide ▴
BP7 N/ABP7 is limited to synonymous or deep intronic variants without predicted splice impact and does not apply to this frameshift deletion. Details ▾Hide ▴
Rule
A synonymous or intronic variant at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
PP5 N/APP5 is not for use in this VCEP. Details ▾Hide ▴
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.348del
- Protein (HGVS p.)
- NP_000305.3:p.(Asp116GlufsTer18)
- GRCh38
- chr10:87933106 AC>A
- GRCh37
- chr10:89692863 AC>A
Gene diagram
Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.
PTENNM_000314.8
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PTEN
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/APTEN PP3 is specified for missense variants using REVEL or for splicing variants with concordant splice predictors. This exonic frameshift deletion is not a missense variant, is not a splice-region variant, and no concordant splicing framework beyond SpliceAI was provided. Details ▾Hide ▴
Rule
PTEN PP3 applies to missense variants with REVEL >0.7 or splicing variants with concordant splice prediction evidence.
Evidence considered
- max SpliceAI delta score 0.00
- variant is exonic frameshift
Sources
BP4 N/APTEN BP4 is specified for synonymous or intronic variants with benign splicing predictions, or missense variants with REVEL <0.5. This variant is an exonic frameshift deletion, so BP4 does not apply. Details ▾Hide ▴
Rule
PTEN BP4 applies to synonymous/intronic variants with benign splice predictions or missense variants with REVEL <0.5.
Evidence considered
- max SpliceAI delta score 0.00
- variant is exonic frameshift
Sources
BP7 N/ABP7 is limited to synonymous or deep intronic variants without predicted splice impact and does not apply to this frameshift deletion. Details ▾Hide ▴
Rule
A synonymous or intronic variant at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- frameshift consequence p.(Asp116GlufsTer18)
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Cancer hotspots
Captured Cancer Hotspots source record
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637575
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_000314.8%3Ac.348del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89692863-AC-A?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87933106-AC-A?dataset=g…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.348d…
- OncoKB ↗www.oncokb.org/gene/PTEN/D116Efs*
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV64292521, n = 2 times).