About STK11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STK11 c.*16+7C>T, p.?
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 Not recorded. 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is rare in population databases, with gnomAD v2.1 AF 0.00639% (8/125122) and gnomAD v4.1 AF 0.00677% (101/1490806), both below the 0.1% PM2 threshold.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Available computational evidence supports no significant impact on splicing. SpliceAI predicts a maximum delta score of 0.01, which is below commonly used splice-impact thresholds; REVEL and BayesDel scores were not available for this noncoding change.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.
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
101 / 1,490,806 alleles
gnomAD v4.1: 101 / 1,490,806 alleles. Recorded AF 6.77486e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.39376e-05; MAF= 0.00639%, 8/125122 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000145709; MAF= 0.01457%, 2/13726 alleles, homozygotes = 0); grpmax FAF= 5.434e-05.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
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 Not recorded, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 5 not met · 14 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The STK11 c.*16+7C>T (p.?) variant has been reported in ClinVar as likely benign by two clinical laboratories, and no expert-panel review was identified.
This variant is present at low frequency in gnomAD, with AF 0.00639% in v2.1 and AF 0.00677% in v4.1; these values remain below the 0.1% PM2 threshold.
In silico splice prediction does not support a damaging effect, with SpliceAI showing a maximum delta score of 0.01, consistent with no significant splice impact.
No criteria match.
Met · 2
PM2 SupportingThis variant is rare in population databases, with gnomAD v2.1 AF 0.00639% (8/125122) and gnomAD v4.1 AF 0.00677% (101/1490806), both below the 0.1% PM2 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 total AF 6.39376e-05.
- gnomAD v4.1 total AF 6.77486e-05.
Sources
BP4 SupportingAvailable computational evidence supports no significant impact on splicing. SpliceAI predicts a maximum delta score of 0.01, which is below commonly used splice-impact thresholds; REVEL and BayesDel scores were not available for this noncoding change. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.0
- DS_AL 0.0
- DS_DG 0.01
- DS_DL 0.0
- max delta 0.01.
- REVEL not found.
- BayesDel not found.
Sources
Not met · 5 · evaluated, threshold not reached
PVS1 STK11 loss of function is an established disease mechanism, but this variant is a noncanonical c.*16+7C>T change in the terminal noncoding region and does not fall within the generic PVS1 null-variant categories of nonsense, frameshift, or canonical +/-1,2 splice variants. Details ▾Hide ▴
Evidence considered
- Gene-level PVS1 eligibility for STK11 is supported.
- Variant-level generic PVS1 scaffold does not support default PVS1 application.
Still missing
- No variant-specific RNA evidence was identified to show transcript loss or a proven loss-of-function splicing effect.
Sources
PM1 This variant lies in the terminal noncoding region, and no evidence was identified that this position is a mutational hotspot or a well-established critical noncoding element with little benign variation. Details ▾Hide ▴
Evidence considered
- Noncoding location with no hotspot evidence.
Still missing
- Need evidence for a pathogenic noncoding hotspot or critical regulatory element at this site.
PP3 Available computational evidence does not support a damaging splice effect. SpliceAI shows a maximum delta score of 0.01, which is below commonly used significance thresholds, and REVEL and BayesDel scores were not available for this noncoding change. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01.
- REVEL not found.
- BayesDel not found.
Still missing
- Additional validated noncoding prediction or RNA data would be needed to support a damaging computational argument.
Sources
BA1 The population frequency does not meet the BA1 threshold. The highest observed population frequency is 0.00827% in gnomAD v4.1, which is below the 1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 highest observed subpopulation AF 0.0000826896.
Sources
BS1 The population frequency does not meet the BS1 threshold. The highest observed population frequency is 0.00827% in gnomAD v4.1, which is below the 0.3% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 best subpopulation AF 0.000145709.
- gnomAD v4.1 best subpopulation AF 0.0000826896.
Sources
Not assessed · 14 · no assessment recorded
PS2 No confirmed de novo occurrence with parental testing was identified for this variant. Details ▾Hide ▴
Evidence considered
- ClinVar summary does not provide de novo evidence.
Still missing
- Need a reported affected individual with confirmed maternity and paternity.
Sources
PS3 No published functional or RNA study was identified showing that this variant damages STK11 function or splicing. Details ▾Hide ▴
Evidence considered
- Only in silico splice prediction was available.
Still missing
- Need validated variant-specific RNA
- minigene
- or other functional assay data.
Sources
PS4 No enrichment data or series of affected individuals carrying this variant were identified. Details ▾Hide ▴
Evidence considered
- ClinVar includes a likely benign submission summary.
- Population observations are present in gnomAD.
Still missing
- Need case-level counts or case-control evidence showing increased prevalence in affected individuals.
Sources
PM6 No probable de novo occurrence was identified for this variant. Details ▾Hide ▴
Evidence considered
- No probable de novo note was available.
Still missing
- Need a reported affected individual with a de novo occurrence lacking full parental confirmation.
Sources
PP1 No segregation data were identified showing that this variant tracks with disease in a family. Details ▾Hide ▴
Evidence considered
- No family segregation evidence was provided.
Still missing
- Need informative meioses demonstrating cosegregation.
Sources
PP4 No case-specific phenotype information was identified to determine whether the clinical presentation is highly specific for an STK11-related disorder. Details ▾Hide ▴
Evidence considered
- No phenotype packet was available in the reviewed files.
Still missing
- Need phenotype details from the tested individual.
PP5 No independent reputable-source pathogenic assertion suitable for PP5 use was identified. Details ▾Hide ▴
Evidence considered
- ClinVar shows a likely benign
- not pathogenic
- submission summary.
Still missing
- Would require a qualifying pathogenic assertion from a reputable source without accessible underlying evidence.
Sources
BS2 Population data show heterozygous carriers but no evidence was identified demonstrating observation in healthy adults at a level sufficient for BS2. Details ▾Hide ▴
Evidence considered
- No homozygotes reported in gnomAD v2.1 or v4.1.
Still missing
- Need validated observations in unaffected adults consistent with a benign interpretation.
Sources
BS3 No well-established functional or RNA study was identified showing that this variant has no damaging effect on STK11 function or splicing. Details ▾Hide ▴
Evidence considered
- Only computational splice prediction was available.
Still missing
- Need robust negative functional or transcript evidence.
Sources
BS4 No nonsegregation data were identified for this variant. Details ▾Hide ▴
Evidence considered
- No family nonsegregation evidence was available.
Still missing
- Need convincing family data showing lack of cosegregation with disease.
Sources
BP2 No phase or co-occurrence data were identified for this variant. Details ▾Hide ▴
Evidence considered
- No co-occurrence data were provided.
Still missing
- Need confirmed in trans or in cis observations with another variant
- as clinically relevant.
Sources
BP3 No evidence was identified that this variant lies within a repetitive region or a region without known function where small variation is common. Details ▾Hide ▴
Evidence considered
- No repetitive-region evidence was available.
Still missing
- Need region-specific annotation supporting a benign repetitive-context interpretation.
BP5 No evidence was identified for an alternate molecular explanation that would make this variant noncontributory to the phenotype. Details ▾Hide ▴
Evidence considered
- No alternate-cause information was available.
Still missing
- Need case-specific alternate-cause data.
BP6 ClinVar reports this variant as likely benign, but no independent reputable-source benign assertion without accessible evidence was identified for BP6 use. Details ▾Hide ▴
Evidence considered
- ClinVar classification is likely benign with criteria provided
- single submitter review status.
Still missing
- Would require a qualifying reputable-source benign assertion if BP6 were to be considered.
Sources
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AThis is a noncoding variant with no defined amino acid substitution, so the same-amino-acid-change rule does not apply. Details ▾Hide ▴
Evidence considered
- Protein consequence is p.?.
PM3 N/ANo recessive disease context or trans observations relevant to PM3 were identified for this variant. Details ▾Hide ▴
Evidence considered
- PM3 is a recessive-phase criterion.
PM4 N/AThis variant does not alter protein length or the reading frame. Details ▾Hide ▴
Evidence considered
- Noncoding variant with protein consequence p.?.
PM5 N/AThis is not a novel missense change at a residue with another established pathogenic missense variant. Details ▾Hide ▴
Evidence considered
- No amino acid substitution is defined.
PP2 N/APP2 is a missense-based criterion and does not apply to this noncoding variant. Details ▾Hide ▴
Evidence considered
- No missense change is present.
BP1 N/ABP1 is a missense-based criterion and does not apply to this noncoding variant. Details ▾Hide ▴
Evidence considered
- No missense change is present.
BP7 N/ABP7 is intended for synonymous variants, and this variant is a noncoding intronic/UTR change rather than a synonymous substitution. Details ▾Hide ▴
Evidence considered
- Variant nomenclature indicates a noncoding intronic/UTR change.
Identifiers
- Gene
- STK11
- Transcript
- NM_000455.5
- Coding (HGVS c.)
- NM_000455.5:c.*16+7C>T
- Protein (HGVS p.)
- NP_000446.1:p.?
- GRCh38
- chr19:1226670 C>T
- GRCh37
- chr19:1226669 C>T
Gene diagram
Every interpreted variant in STK11, mapped onto the exon structure of NM_000455.5. Select a row to find it on the plot.
STK11NM_000455.5
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 STK11
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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
101 / 1,490,806 alleles
AF 6.77e-05 · 0 homozygotes · FAF 6.88e-05
gnomAD v2.1
8 / 125,122 alleles
AF 6.39e-05 · 0 homozygotes · FAF 5.43e-05
By genetic ancestry
gnomAD v4.1
AF 6.8e-05 · 101 / 1,490,806 alleles · 0 hom · FAF 6.9e-05
| European (non-Finnish)93 / 1,124,688 | 8.3e-05 |
| East Asian3 / 39,896 | 7.5e-05 |
| African/African American3 / 70,684 | 4.2e-05 |
| Remaining individuals1 / 57,670 | 1.7e-05 |
| South Asian1 / 76,142 | 1.3e-05 |
0 alternate alleles recorded in 5 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 6.4e-05 · 8 / 125,122 alleles · 0 hom · FAF 5.4e-05
| African/African American2 / 13,726 | 0.00015 |
| European (non-Finnish)6 / 51,282 | 0.00012 |
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.77486e-05; MAF= 0.00677%, 101/1490806 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.26896e-05; MAF= 0.00827%, 93/1124688 alleles, homozygotes = 0); grpmax FAF= 6.881e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.39376e-05; MAF= 0.00639%, 8/125122 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000145709; MAF= 0.01457%, 2/13726 alleles, homozygotes = 0); grpmax FAF= 5.434e-05.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingAvailable computational evidence supports no significant impact on splicing. SpliceAI predicts a maximum delta score of 0.01, which is below commonly used splice-impact thresholds; REVEL and BayesDel scores were not available for this noncoding change. Details ▾Hide ▴
Evidence considered
- SpliceAI DS_AG 0.0
- DS_AL 0.0
- DS_DG 0.01
- DS_DL 0.0
- max delta 0.01.
- REVEL not found.
- BayesDel not found.
Sources
PP3 Available computational evidence does not support a damaging splice effect. SpliceAI shows a maximum delta score of 0.01, which is below commonly used significance thresholds, and REVEL and BayesDel scores were not available for this noncoding change. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score 0.01.
- REVEL not found.
- BayesDel not found.
Still missing
- Additional validated noncoding prediction or RNA data would be needed to support a damaging computational argument.
Sources
BP7 N/ABP7 is intended for synonymous variants, and this variant is a noncoding intronic/UTR change rather than a synonymous substitution. Details ▾Hide ▴
Evidence considered
- Variant nomenclature indicates a noncoding intronic/UTR change.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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
101 / 1,490,806 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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/378682/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/19-1226669-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr19-1226670-C-T?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000455.5%3Ac.%2A1…
- OncoKB ↗www.oncokb.org/gene/STK11/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=STK11+c.*16+7C%3ET
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= 6.77486e-05; MAF= 0.00677%, 101/1490806 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.26896e-05; MAF= 0.00827%, 93/1124688 alleles, homozygotes = 0); grpmax FAF= 6.881e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.39376e-05; MAF= 0.00639%, 8/125122 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000145709; MAF= 0.01457%, 2/13726 alleles, homozygotes = 0); grpmax FAF= 5.434e-05.
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).