About PTEN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTEN c.-307C>G, p.?
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign 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: 0
Benign evidence criteria: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BS1Strong
BS1 · strong
Population frequency meets the PTEN BS1 strong threshold. The highest observed gnomAD v4.1 subpopulation allele frequency is 1.23e-04 in Ashkenazi Jewish individuals, which falls within the PTEN BS1 strong range of 4.3e-05 to 5.6e-04.
Recorded classification: Likely benign
Richards et.al., 2015 - Combining rules v3.2.0 criteria-combination framework: matched Rule20 (1 Benign.Strong) with applied criteria: BS1 strong; maps to Likely Benign.
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
3 / 565,266 alleles
gnomAD v4.1: 3 / 565,266 alleles. Recorded AF 5.30724e-06. Recorded homozygote count 0.
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 ↗
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
COSMIC ↗
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: 1 met · 5 not met · 9 not assessed · 13 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 c.-307C>G (NP_000305.3:p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.
This variant is absent from gnomAD v2.1, but in gnomAD v4.1 it is present at an overall allele frequency of 5.31e-06 and reaches 1.23e-04 in the Ashkenazi Jewish population, which meets the PTEN BS1 strong frequency range and is above the PTEN PM2 subpopulation threshold.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00, and no PTEN-specific computational evidence supporting a deleterious effect was identified.
No criteria match.
Met · 1
BS1 StrongPopulation frequency meets the PTEN BS1 strong threshold. The highest observed gnomAD v4.1 subpopulation allele frequency is 1.23e-04 in Ashkenazi Jewish individuals, which falls within the PTEN BS1 strong range of 4.3e-05 to 5.6e-04. Details ▾Hide ▴
Rule
PTEN BS1_Strong applies for filtering allele frequency from 0.000043 up to 0.00056.
Evidence considered
- gnomAD v4.1 highest subpopulation AF 0.000122745 (2/16294 Ashkenazi Jewish alleles).
Sources
Not met · 5 · evaluated, threshold not reached
PM2 Population frequency does not meet the PTEN PM2_Supporting threshold. Although the overall gnomAD v4.1 allele frequency is 5.31e-06, below the <1.0e-05 threshold, the highest observed subpopulation frequency is 1.23e-04 in Ashkenazi Jewish individuals with 2 alleles, which is above the required <2.0e-05 subpopulation threshold when multiple alleles are present. Details ▾Hide ▴
Rule
PTEN PM2_Supporting requires AF <0.00001 and, if multiple alleles are present in any subpopulation, subpopulation AF <0.00002.
Evidence considered
- gnomAD v2.1: absent.
- gnomAD v4.1: 3/565266 alleles overall
- highest subpopulation AF 0.000122745 in Ashkenazi Jewish individuals (2/16294).
Sources
PP3 Available computational evidence does not support a deleterious splicing effect under the PTEN PP3 rule. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and this upstream noncoding variant has no REVEL score because it is not missense. Details ▾Hide ▴
Rule
PTEN PP3 uses concordant splicing prediction for splicing variants or REVEL >0.7 for missense variants.
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL not available because the variant is not missense.
Still missing
- No PTEN-specified additional computational evidence supporting a damaging effect for this promoter-region substitution was identified.
Sources
BA1 Population frequency does not reach the PTEN BA1 threshold. The highest observed gnomAD v4.1 subpopulation allele frequency is 1.23e-04, which is below the BA1 cutoff of >5.6e-04. Details ▾Hide ▴
Rule
PTEN BA1 requires gnomAD filtering allele frequency >0.00056.
Evidence considered
- Highest observed subpopulation AF is 0.000122745 in Ashkenazi Jewish individuals.
Sources
BS2 Available population data do not support BS2 because no homozygous individuals were reported in gnomAD for this variant. Details ▾Hide ▴
Rule
PTEN BS2 requires homozygous observation in a healthy or PHTS-unaffected individual.
Evidence considered
- gnomAD v4.1 reports 0 homozygotes.
Still missing
- No healthy homozygous observation or PTEN-unaffected homozygous individual was identified.
Sources
BP4 Available computational evidence does not satisfy the PTEN BP4 rule for a benign prediction. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, but the PTEN BP4 specification requires concordant splicing predictions for qualifying splicing-region variants or REVEL <0.5 for missense variants, and this upstream noncoding substitution is neither. Details ▾Hide ▴
Rule
PTEN BP4 uses concordant splicing prediction for splicing variants or REVEL <0.5 for missense variants.
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL not available because the variant is not missense.
Still missing
- No PTEN-specified benign computational framework for promoter-region substitutions was identified.
Sources
Not assessed · 9 · no assessment recorded
PS2 No confirmed de novo occurrence was identified for this variant, so PS2 cannot be assessed from the available evidence. Details ▾Hide ▴
Rule
PTEN PS2 requires confirmed de novo occurrence in a patient with disease and no family history.
Evidence considered
- No ClinVar record or linked case data were identified for this exact variant.
Still missing
- No trio data or confirmed maternity/paternity information was identified.
Sources
PS3 No well-established functional study was identified showing that this exact upstream variant damages PTEN function or splicing. The PTEN phosphatase saturation assay is specified for missense variants and does not address this promoter-region substitution. Details ▾Hide ▴
Rule
PTEN PS3 requires a qualifying damaging functional study.
Evidence considered
- PTEN VCEP allows PS3 from validated splicing assays or PTEN missense phosphatase assay data.
- The available PTEN functional assay file is restricted to missense variants.
Still missing
- No exact-variant promoter
- RNA
- or expression assay result was identified.
Sources
cspec ↗vcep_mmc2
PS4 No affected-proband series, enrichment data, or case-control evidence was identified for this exact variant, so PS4 is not established. Details ▾Hide ▴
Rule
PTEN PS4 requires proband specificity scoring or significant enrichment in affected individuals.
Evidence considered
- Variant is absent from ClinVar and no case-based evidence was identified.
Still missing
- No proband count or phenotype-specific observation data were identified.
Sources
PM6 No presumed de novo observation was identified for this variant, so PM6 cannot be applied. Details ▾Hide ▴
PP1 No segregation data were identified for this variant, so PP1 cannot be assessed. Details ▾Hide ▴
BS3 No functional study was identified showing that this exact upstream variant has no damaging effect on PTEN function or splicing, so BS3 cannot be applied. Details ▾Hide ▴
Rule
PTEN BS3 requires a qualifying functional study showing no damaging effect.
Evidence considered
- PTEN benign functional rule is defined for qualifying splicing assays or missense phosphatase assay data
- and no exact-variant benign assay evidence was identified.
Still missing
- No exact-variant benign promoter
- RNA
- or expression assay result was identified.
Sources
cspec ↗vcep_mmc2
BS4 No lack-of-segregation evidence was identified for this variant, so BS4 cannot be assessed. Details ▾Hide ▴
BP2 No phase data were identified showing this variant in trans with a pathogenic PTEN variant or repeatedly in cis/phase unknown with different pathogenic PTEN variants, so BP2 cannot be assessed. Details ▾Hide ▴
BP5 No alternate highly penetrant molecular diagnosis with a non-overlapping phenotype was identified, so BP5 cannot be assessed. Details ▾Hide ▴
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is an upstream noncoding substitution and does not fall into the PTEN PVS1 decision tree categories for nonsense, frameshift, canonical +/-1,2 splice-site, or qualifying exon-level loss-of-function variants. Available evidence does not support applying PVS1 to this promoter-region change. Details ▾Hide ▴
Rule
PTEN VCEP PVS1 decision tree; generic PVS1 scaffold does not apply to this upstream substitution.
Evidence considered
- PTEN has an established loss-of-function disease mechanism
- but this variant is outside the PTEN PVS1 null-variant buckets.
- Generic PVS1 scaffold classifies the variant bucket as 'other' and does not recommend generic PVS1 application.
Still missing
- No direct evidence was identified showing that this exact upstream change causes a null PTEN allele or equivalent transcript loss.
Sources
PS1 N/AThis criterion is not applicable because the variant does not define an amino acid change, and no same-nucleotide pathogenic splicing comparator was identified for this upstream substitution. Details ▾Hide ▴
Rule
PTEN PS1 applies to the same amino acid change as a known pathogenic variant or an equivalent pathogenic splicing comparison at the same nucleotide.
Evidence considered
- Protein consequence is unresolved (p.?).
- Variant is not a missense or established splice-equivalent change.
Sources
PM1 N/AThis criterion is not applicable because the PTEN PM1 specification is defined for established protein catalytic motifs, and this upstream noncoding variant is outside those residues. Details ▾Hide ▴
Rule
PTEN PM1 applies to variants in defined catalytic motifs.
Evidence considered
- PTEN PM1 critical motifs are specified at protein residues 90-94
- 123-130
- and 166-168.
- This variant has no protein residue assignment.
Sources
PM3 N/AThis criterion is not applicable in the PTEN specification. Details ▾Hide ▴
Rule
PTEN VCEP marks PM3 not applicable.
Evidence considered
- PTEN VCEP lists PM3 as not applicable.
Sources
PM4 N/AThis upstream substitution does not cause a protein length change, in-frame insertion/deletion, or stop-loss event, so PM4 is not applicable. Details ▾Hide ▴
Rule
PTEN PM4 applies to qualifying protein length changes.
Evidence considered
- Variant is a noncoding upstream single-nucleotide substitution.
Sources
PM5 N/AThis criterion is not applicable because the PTEN PM5 rule uses classic same-residue missense logic, and this variant is not missense-like. Details ▾Hide ▴
Rule
PTEN PM5 applies to a missense change at an amino acid residue with a different pathogenic or likely pathogenic missense comparator.
Evidence considered
- PM5 candidate review found the variant is not eligible for classic same-residue missense PM5 analysis.
Sources
pm5_candidatescspec ↗
PP2 N/AThis criterion is not applicable because PP2 is a missense-based rule and this variant does not produce a missense change. Details ▾Hide ▴
Rule
PTEN PP2 applies to missense variants.
Evidence considered
- Protein consequence is unresolved and not missense.
Sources
PP4 N/AThis criterion is not applicable in the PTEN specification because phenotype specificity is incorporated into PS4. Details ▾Hide ▴
Rule
PTEN VCEP marks PP4 not applicable.
Evidence considered
- PTEN VCEP lists PP4 as not applicable.
Sources
PP5 N/AThis criterion is not applicable in the PTEN specification. Details ▾Hide ▴
Rule
PTEN VCEP marks PP5 not applicable.
Evidence considered
- PTEN VCEP lists PP5 as not applicable.
Sources
BP1 N/AThis criterion is not applicable in the PTEN specification. Details ▾Hide ▴
Rule
PTEN VCEP marks BP1 not applicable.
Evidence considered
- PTEN VCEP lists BP1 as not applicable.
Sources
BP3 N/AThis criterion is not applicable in the PTEN specification. Details ▾Hide ▴
Rule
PTEN VCEP marks BP3 not applicable.
Evidence considered
- PTEN VCEP lists BP3 as not applicable.
Sources
BP6 N/AThis criterion is not applicable in the PTEN specification. Details ▾Hide ▴
Rule
PTEN VCEP marks BP6 not applicable.
Evidence considered
- PTEN VCEP lists BP6 as not applicable.
Sources
BP7 N/AThis criterion is not applicable because the variant is not a synonymous variant and is not an intronic variant at or beyond +7/-21. Details ▾Hide ▴
Rule
PTEN BP7 applies to synonymous or specified intronic variants with no predicted splice impact.
Evidence considered
- Variant is an upstream noncoding substitution.
- SpliceAI shows no splice impact
- but BP7 is defined for synonymous or qualifying intronic variants.
Sources
Identifiers
- Gene
- PTEN
- Transcript
- NM_000314.8
- Coding (HGVS c.)
- NM_000314.8:c.-307C>G
- Protein (HGVS p.)
- NP_000305.3:p.?
- GRCh38
- chr10:87864163 C>G
- GRCh37
- chr10:89623920 C>G
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
3 / 565,266 alleles
AF 5.31e-06 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 5.3e-06 · 3 / 565,266 alleles · 0 hom
| Ashkenazi Jewish2 / 16,294 | 0.00012 |
| European (non-Finnish)1 / 316,368 | 3.2e-06 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, African/African American.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 5.30724e-06; MAF= 0.00053%, 3/565266 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000122745; MAF= 0.01227%, 2/16294 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Available computational evidence does not support a deleterious splicing effect under the PTEN PP3 rule. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and this upstream noncoding variant has no REVEL score because it is not missense. Details ▾Hide ▴
Rule
PTEN PP3 uses concordant splicing prediction for splicing variants or REVEL >0.7 for missense variants.
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL not available because the variant is not missense.
Still missing
- No PTEN-specified additional computational evidence supporting a damaging effect for this promoter-region substitution was identified.
Sources
BP4 Available computational evidence does not satisfy the PTEN BP4 rule for a benign prediction. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, but the PTEN BP4 specification requires concordant splicing predictions for qualifying splicing-region variants or REVEL <0.5 for missense variants, and this upstream noncoding substitution is neither. Details ▾Hide ▴
Rule
PTEN BP4 uses concordant splicing prediction for splicing variants or REVEL <0.5 for missense variants.
Evidence considered
- SpliceAI max delta score 0.00.
- REVEL not available because the variant is not missense.
Still missing
- No PTEN-specified benign computational framework for promoter-region substitutions was identified.
Sources
BP7 N/AThis criterion is not applicable because the variant is not a synonymous variant and is not an intronic variant at or beyond +7/-21. Details ▾Hide ▴
Rule
PTEN BP7 applies to synonymous or specified intronic variants with no predicted splice impact.
Evidence considered
- Variant is an upstream noncoding substitution.
- SpliceAI shows no splice impact
- but BP7 is defined for synonymous or qualifying intronic variants.
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
3 / 565,266 recorded alleles
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
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.-307C%3EG
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/10-89623920-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr10-87864163-C-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000314.8%3Ac.-307…
- OncoKB ↗www.oncokb.org/gene/PTEN/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PTEN+c.-307C%3EG
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 5.30724e-06; MAF= 0.00053%, 3/565266 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000122745; MAF= 0.01227%, 2/16294 alleles, homozygotes = 0).
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).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).