About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.1027-1G>C, p.?
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Strong
PVS1 · strong
PTEN-specific PVS1 guidance supports PVS1_Strong for this canonical splice acceptor variant at NM_000314.8:c.1027-1G>C. The affected site is the acceptor of exon 9; exon 9 loss preserves reading frame, and the PTEN decision tree explicitly treats entire exon 9 as a critical altered region for GT-AG splice-site variants.
PS1Strong
PS1 · strong
PTEN PS1_Strong is met because a different substitution at the same nucleotide position is already established as pathogenic in ClinVar (NM_000314.8:c.1027-1G>A), and SpliceAI predicts equal splice acceptor loss for the queried variant and the known pathogenic same-position variant (DS_AL 0.99 for both).
PM2Supporting
PM2 · supporting
PM2_Supporting is met because the variant is absent from both gnomAD v2.1 and gnomAD v4.1, satisfying the PTEN EP ultra-rare population threshold.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
PTEN VCEP v3.2.0 ACMG/AMP categorical combination: PVS1_Strong + PS1_Strong + PM2_Supporting.
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.
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 ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
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: 3 met · 3 not met · 11 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The PTEN-specific PVS1 decision tree supports PVS1_Strong for this canonical splice acceptor variant because it affects the exon 9 acceptor of NM_000314.8, and preserved-frame loss of entire exon 9 is explicitly treated as a critical altered region in PTEN.
PS1_Strong is met because ClinVar contains a same-nucleotide pathogenic splicing variant at NM_000314.8:c.1027-1G>A.
The queried variant shows equal predicted splice acceptor loss to the known pathogenic same-position variant by SpliceAI (DS_AL 0.99), satisfying the PTEN same-position splicing use of PS1.
PM2_Supporting is met because the variant is absent from both gnomAD v2.1 and gnomAD v4.1.
No assembled RNA assay, de novo series, segregation dataset, or PTEN PS4 phenotype-scored case series was available to upgrade beyond the current evidence combination.
No criteria match.
Met · 3
PVS1 StrongPTEN-specific PVS1 guidance supports PVS1_Strong for this canonical splice acceptor variant at NM_000314.8:c.1027-1G>C. The affected site is the acceptor of exon 9; exon 9 loss preserves reading frame, and the PTEN decision tree explicitly treats entire exon 9 as a critical altered region for GT-AG splice-site variants. Details ▾Hide ▴
Rule
Use PTEN PVS1 decision tree for canonical splice-site variants.
Evidence considered
- Variant is a canonical -1 splice acceptor change in NM_000314.8
- PTEN PVS1 decision tree lists preserved-frame loss of entire exon 9 as PVS1_Strong
Sources
vcep_p_v_s_1___d_e_c_i_s_i_o_n_t_r_e_e___p_t_e_ncspec ↗
PS1 StrongPTEN PS1_Strong is met because a different substitution at the same nucleotide position is already established as pathogenic in ClinVar (NM_000314.8:c.1027-1G>A), and SpliceAI predicts equal splice acceptor loss for the queried variant and the known pathogenic same-position variant (DS_AL 0.99 for both). Details ▾Hide ▴
Rule
Different variant at the same nucleotide position as a pathogenic splicing variant, where in silico models predict impact equal to or greater than the known pathogenic variant.
Evidence considered
- ClinVar same-position pathogenic variant: NM_000314.8:c.1027-1G>A
- SpliceAI acceptor-loss score for NM_000314.8:c.1027-1G>C = 0.99
- Equal SpliceAI acceptor-loss score was confirmed for NM_000314.8:c.1027-1G>A
Sources
PM2 SupportingPM2_Supporting is met because the variant is absent from both gnomAD v2.1 and gnomAD v4.1, satisfying the PTEN EP ultra-rare population threshold. Details ▾Hide ▴
Rule
Absent or ultra-rare in gnomAD below PTEN EP PM2 thresholds.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
Sources
Not met · 3 · evaluated, threshold not reached
BA1 BA1 is not met because the variant is absent from gnomAD. Details ▾Hide ▴
Rule
gnomAD filtering allele frequency >0.00056 (0.056%).
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
Sources
BS1 BS1 is not met because the variant is absent from gnomAD rather than exceeding PTEN benign frequency thresholds. Details ▾Hide ▴
Rule
Allele frequency above PTEN BS1 thresholds.
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
Sources
BP4 BP4 is not met because SpliceAI predicts strong splice impact (max delta 0.99), and PTEN BP4 for splicing additionally requires benign no-impact concordance of SpliceAI and VarSeak. Details ▾Hide ▴
Rule
For PTEN splicing variants, BP4 requires no-impact concordance of SpliceAI and VarSeak.
Evidence considered
- SpliceAI max delta = 0.99
Sources
Not assessed · 11 · no assessment recorded
PS2 No confirmed de novo evidence was assembled in the reviewed workspace. Details ▾Hide ▴
Rule
De novo occurrence with maternity and paternity confirmed.
Evidence considered
- No de novo case data in case workspace
Still missing
- Confirmed maternity and paternity testing with de novo occurrence
Sources
PS3 No PTEN RNA, minigene, or other splicing assay demonstrating abnormal splicing for this variant was assembled. The PTEN mmc2 functional file is missense-specific and not applicable to this splice variant. Details ▾Hide ▴
Rule
RNA, mini-gene, or other assay showing impact on splicing.
Evidence considered
- No RNA assay in workspace
- mmc2 guidance applies to missense variants
Still missing
- Variant-specific RNA or splicing functional assay
Sources
cspec ↗vcep_m_m_c_2
PS4 The workspace did not provide PTEN-scored proband phenotype specificity data or a qualifying case-control dataset to calculate PS4. Details ▾Hide ▴
PM6 No assumed de novo evidence was assembled in the workspace. Details ▾Hide ▴
Rule
Assumed de novo occurrence in a patient with disease and no family history.
Evidence considered
- No de novo case packet
Still missing
- Assumed de novo proband data without family history
Sources
PP1 No segregation data were assembled. Details ▾Hide ▴
Rule
Co-segregation with disease in multiple affected family members.
Evidence considered
- No family segregation evidence in workspace
Still missing
- Segregation across informative meioses
Sources
PP3 SpliceAI strongly predicts splice impact (max delta 0.99), but the PTEN EP splicing PP3 rule requires concordance of SpliceAI and VarSeak. VarSeak evidence was not assembled in this workspace, so PP3 was not applied. Details ▾Hide ▴
Rule
For PTEN splicing variants, PP3 requires concordance of SpliceAI and VarSeak.
Evidence considered
- SpliceAI max delta = 0.99
- No VarSeak result in workspace
Still missing
- VarSeak result showing concordant pathogenic splice prediction
Sources
BS2 No homozygous observations in healthy or PTEN-unaffected individuals were assembled. Details ▾Hide ▴
Rule
Observed in the homozygous state in a healthy or PHTS-unaffected individual.
Evidence considered
- No BS2-ready observations in workspace
Still missing
- Documented homozygous healthy or PTEN-unaffected observations
Sources
BS3 No RNA or other splicing assay demonstrating no impact on splicing was assembled. Details ▾Hide ▴
Rule
Functional study showing no damaging effect on protein function or splicing.
Evidence considered
- No benign functional splicing study in workspace
- mmc2 guidance is missense-specific
Still missing
- Variant-specific benign RNA/splicing assay
Sources
cspec ↗vcep_m_m_c_2
BS4 No lack-of-segregation evidence was assembled. Details ▾Hide ▴
Rule
Lack of segregation in affected members of one or more families.
Evidence considered
- No segregation packet
Still missing
- Family data showing lack of segregation
Sources
BP2 No phase data with other pathogenic/likely pathogenic PTEN variants were assembled. Details ▾Hide ▴
Rule
Observed in trans with a pathogenic/likely pathogenic PTEN variant or sufficient cis/phase-unknown observations.
Evidence considered
- No BP2-ready phase observations in workspace
Still missing
- Trans/cis or phase-unknown observations with qualifying PTEN variants
Sources
BP5 The workspace did not document at least two cases with an alternate highly penetrant diagnosis and non-overlapping PTEN phenotype. Details ▾Hide ▴
Rule
Variant found in a case with an alternate molecular basis for disease under PTEN EP restrictions.
Evidence considered
- No BP5-ready alternate diagnosis data in workspace
Still missing
- Qualifying alternate molecular diagnoses with phenotype non-overlap
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PM1 N/APM1 in PTEN is defined for missense changes in catalytic motifs at residues 90-94, 123-130, and 166-168; this is a splice acceptor variant outside that missense/domain use case. Details ▾Hide ▴
Rule
PTEN PM1 is limited to catalytic motif residues 90-94, 123-130, and 166-168.
Evidence considered
- Variant class is splice acceptor, not missense in PTEN catalytic motif
Sources
PM3 N/APM3 is not applicable in the PTEN VCEP framework. Details ▾Hide ▴
PM4 N/APM4 is reserved for in-frame indels or stop-loss variants, not for this canonical splice acceptor SNV. Details ▾Hide ▴
Rule
Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.
Evidence considered
- Variant class is intronic splice acceptor SNV
Sources
PM5 N/APM5 is a missense-specific rule and does not apply to this splice acceptor variant. Details ▾Hide ▴
Rule
Missense change at a residue with a different pathogenic missense change previously observed.
Evidence considered
- Variant is not missense
Sources
PP2 N/APP2 is a missense-context rule and does not apply to this splice acceptor variant. Details ▾Hide ▴
Rule
Missense variant in a gene with low benign missense rate and common missense disease mechanism.
Evidence considered
- Variant is not missense
Sources
PP4 N/APP4 is not applicable in the PTEN VCEP framework because phenotype specificity is incorporated into PS4 specifications. Details ▾Hide ▴
PP5 N/APP5 is not for use in this PTEN VCEP framework. Details ▾Hide ▴
BP1 N/ABP1 is not applicable to PTEN in this VCEP framework. Details ▾Hide ▴
BP3 N/ABP3 is not applicable to PTEN in this VCEP framework. Details ▾Hide ▴
BP6 N/ABP6 is not for use in this PTEN VCEP framework. Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous variants or intronic variants at or beyond +7/-21 with no splice impact; this variant is a canonical -1 splice acceptor change. Details ▾Hide ▴
Rule
A synonymous or intronic variant at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- Variant is c.1027-1G>C
- SpliceAI predicts strong splice impact
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.1027-1G>C
- Protein (HGVS p.)
- NP_000305.3:p.?
- GRCh38
- chr10:87965286 G>C
- GRCh37
- chr10:89725043 G>C
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 |
|---|
Statements
No population statements were recorded.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 BP4 is not met because SpliceAI predicts strong splice impact (max delta 0.99), and PTEN BP4 for splicing additionally requires benign no-impact concordance of SpliceAI and VarSeak. Details ▾Hide ▴
Rule
For PTEN splicing variants, BP4 requires no-impact concordance of SpliceAI and VarSeak.
Evidence considered
- SpliceAI max delta = 0.99
Sources
PP3 SpliceAI strongly predicts splice impact (max delta 0.99), but the PTEN EP splicing PP3 rule requires concordance of SpliceAI and VarSeak. VarSeak evidence was not assembled in this workspace, so PP3 was not applied. Details ▾Hide ▴
Rule
For PTEN splicing variants, PP3 requires concordance of SpliceAI and VarSeak.
Evidence considered
- SpliceAI max delta = 0.99
- No VarSeak result in workspace
Still missing
- VarSeak result showing concordant pathogenic splice prediction
Sources
BP7 N/ABP7 applies only to synonymous variants or intronic variants at or beyond +7/-21 with no splice impact; this variant is a canonical -1 splice acceptor change. Details ▾Hide ▴
Rule
A synonymous or intronic variant at or beyond +7/-21 with no predicted splice impact.
Evidence considered
- Variant is c.1027-1G>C
- SpliceAI predicts strong splice impact
Sources
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99).
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
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/variation/481153/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89725043-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87965286-G-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.1027…
- OncoKB ↗www.oncokb.org/gene/PTEN
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
ClinVar
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory) and as Likely pathogenic (1 clinical laboratory).
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99).
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV64298429, n = 5 times).