About the gene
No gene-level summary was recorded for this case.
Previous versions
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: 0
Benign evidence criteria: 0
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
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: none; combination = no applied criteria, which maps to VUS.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
No screenshot for this evidence
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
No listed criterion applied
gnomAD-Canada ↗
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
No screenshot for this evidence
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
No screenshot for this evidence
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 0 met · 0 not met · 25 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
No ACMG/AMP criteria could be met or ruled out for NM_000077.5:c.290A>T due to a critical normalization failure during case preparation: VariantValidator was unavailable and the gene, genomic coordinates, protein consequence, and all downstream evidence sources (gnomAD v2.1/v4.1, ClinVar, REVEL, BayesDel, SpliceAI, COSMIC, OncoKB, Hotspots, literature) could not be resolved. The variant cannot be classified and requires complete re-analysis when normalization services are available.
No criteria match.
Not assessed · 25 · no assessment recorded
PVS1 Gene could not be resolved during normalization (VariantValidator unavailable); loss-of-function mechanism eligibility and variant class (nonsense/frameshift/canonical splice) could not be determined. PVS1 gene gate is manual_review_required. Details ▾Hide ▴
Evidence considered
- Prefetch normalization failed: no gene
- no coordinates
- no protein consequence resolved.
Still missing
- Gene identity
- Variant class/substitution type
- Gene-level LOF mechanism eligibility
- Exon location and nonsense-mediated decay potential
PS1 No ClinVar data available to identify a known pathogenic variant with the same amino acid change; protein consequence could not be resolved during normalization. Details ▾Hide ▴
Evidence considered
- ClinVar query failed: normalization did not resolve gene or coordinates.
Still missing
- Protein consequence (HGVS p. notation)
- ClinVar pathogenic variants at the same residue
PS2 No literature or database evidence of de novo occurrence for this variant was identified; no publications were retrieved for review. Details ▾Hide ▴
Evidence considered
- No PMIDs found across evidence sources
- exploratory search failed due to missing gene.
Still missing
- De novo case reports
- Parental confirmation studies
PS3 No functional studies were identified for this variant; no publications, OncoKB, or ClinVar functional evidence available. Details ▾Hide ▴
Evidence considered
- No functional data in evidence_brief
- literature_pass (0 PMIDs)
- or ClinVar.
Still missing
- In vitro or in vivo functional assay data for this specific variant
PS4 No prevalence or case-control data available; no ClinVar submissions, no publications, and no cohort data retrieved. Details ▾Hide ▴
Evidence considered
- No case/control data in evidence sources.
Still missing
- Affected vs. control population counts
- Odds ratio or case enrichment data
PM1 Gene and protein domain architecture could not be resolved; the variant's location relative to known mutational hotspots or critical functional domains is unknown. Details ▾Hide ▴
Evidence considered
- Gene unknown
- no domain or hotspot information available.
Still missing
- Gene identity
- Protein domain map
- Known mutational hotspot or critical domain data
PM2 gnomAD v2.1 and v4.1 queries failed because normalization did not resolve genomic coordinates. gnomAD-Canada returned AC=0/AN=0 (no coverage), not a true absence call. Population frequency cannot be determined. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: no data (normalization failure)
- gnomAD v4.1: no data (normalization failure)
- gnomAD-Canada: AC=0
- AN=0 (no coverage
- not a true absence)
Still missing
- gnomAD v2.1 allele frequency
- gnomAD v4.1 allele frequency
- Any other population database frequency
PM5 Protein residue context could not be determined; automatic PM5 candidate harvesting was skipped because classic same-residue missense semantics could not be confirmed. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: eligible_for_classic_pm5_search=false
- recommendation level=not_applicable.
Still missing
- Protein consequence of this variant
- ClinVar pathogenic missense variants at the same residue
PM6 No de novo reports (with or without paternity confirmation) were identified for this variant in any database or publication source. Details ▾Hide ▴
Evidence considered
- No de novo data in any evidence source.
Still missing
- De novo reports with maternity/paternity confirmation
PP1 No cosegregation data available; no family studies or pedigrees identified for this variant. Details ▾Hide ▴
Evidence considered
- No cosegregation data in evidence sources.
Still missing
- Family cosegregation data
- LOD scores
PP2 Cannot assess whether this is a missense variant in a gene with a low rate of benign missense variation — gene not identified and HCI prior score unavailable. Details ▾Hide ▴
Evidence considered
- Gene unknown
- HCI prior skipped (no gene).
Still missing
- Gene identity
- Missense constraint metrics (Z-score
- HCI prior)
PP3 No in silico scores available: REVEL, BayesDel, SpliceAI, and HCI prior all failed or were skipped because genomic coordinates could not be resolved. Details ▾Hide ▴
Evidence considered
- REVEL: skipped (no coords)
- BayesDel: skipped (no coords)
- SpliceAI: max_delta=null
- HCI prior: skipped (no gene)
Still missing
- REVEL score
- BayesDel score
- SpliceAI delta scores
- Multiple in silico algorithms supporting a deleterious effect
PP4 No phenotype data available; no patient descriptions, clinical presentations, or disease associations could be evaluated. Details ▾Hide ▴
Evidence considered
- No phenotype data in any evidence source.
Still missing
- Patient phenotype information
- Disease-gene association for the variant's clinical context
PP5 No ClinVar submissions and no publications reporting this variant as pathogenic from a reputable source. Details ▾Hide ▴
Evidence considered
- ClinVar: no variation IDs
- no classification
- zero submitters.
- Literature: 0 PMIDs.
Still missing
- ClinVar or literature reports with pathogenic assertion
BA1 Population allele frequency cannot be determined; gnomAD v2.1 and v4.1 queries failed due to normalization failure. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 and v4.1: no data.
Still missing
- Population allele frequency from major databases
BS1 Population allele frequency cannot be determined; gnomAD v2.1 and v4.1 queries failed due to normalization failure. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 and v4.1: no data.
Still missing
- Population allele frequency for comparison against disease prevalence
BS2 No data on observation in healthy adult individuals; no cohort or control data available. Details ▾Hide ▴
Evidence considered
- No healthy control observation data.
Still missing
- Data on variant presence in healthy adults without the associated disease
BS3 No functional studies identified showing no deleterious effect; no publications, OncoKB, or functional assay data available. Details ▾Hide ▴
Evidence considered
- No functional data in any evidence source.
Still missing
- Well-established in vitro or in vivo functional studies demonstrating no damaging effect
BS4 No segregation data available to evaluate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
- No family or segregation data.
Still missing
- Family segregation data showing non-segregation with disease
BP1 Cannot determine if this is a missense variant in a gene where primarily truncating variants cause disease; gene identity and disease mechanism unknown. Details ▾Hide ▴
Evidence considered
- Gene unknown
- disease mechanism not established.
Still missing
- Gene identity
- Disease mechanism (truncating vs. missense spectrum)
BP2 No data on observation in trans with a known pathogenic variant; no phase or genotype data available. Details ▾Hide ▴
Evidence considered
- No phase or trans-configuration data.
Still missing
- Observation in trans with a pathogenic variant in a recessive disorder context
BP4 No in silico scores available: REVEL, BayesDel, and SpliceAI all failed or were skipped because genomic coordinates and gene could not be resolved. Details ▾Hide ▴
Evidence considered
- REVEL: skipped
- BayesDel: skipped
- SpliceAI: no data
Still missing
- Multiple in silico algorithms supporting a benign effect
BP5 No data available on cases where this variant is found with an alternate molecular cause for the phenotype. Details ▾Hide ▴
Evidence considered
- No alternate molecular cause data.
Still missing
- Observation in cases with a definitive alternate genetic diagnosis
BP6 No ClinVar submissions or publications reporting this variant as benign from a reputable source. Details ▾Hide ▴
Evidence considered
- ClinVar: no variation IDs
- no classification
- zero submitters.
- Literature: 0 PMIDs.
Still missing
- Reputable source reporting the variant as benign
PS5 Requires a reported pathogenic variant at the same nucleotide position from a reputable source; no ClinVar or literature data available. Details ▾Hide ▴
Evidence considered
- No ClinVar or publication data for variants at this nucleotide position.
Still missing
- Pathogenic variant reports at c.290 in NM_000077.5
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 N/ANo trans/cis phase data available and no evidence of recessive disorder context; PM3 requires observation in trans with a pathogenic variant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AThis variant is a substitution, not an in-frame indel or stop-loss variant; PM4 applies only to protein-length-altering non-null variants. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis variant is a substitution, not an in-frame indel; BP3 applies only to in-frame deletions/insertions in repetitive regions without a known function. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is a substitution variant that is highly unlikely to be synonymous and lacks splice prediction data; BP7 is reserved for synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Coding (HGVS c.)
- NM_000077.5:c.290A>T
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
No population statements were recorded.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 No in silico scores available: REVEL, BayesDel, SpliceAI, and HCI prior all failed or were skipped because genomic coordinates could not be resolved. Details ▾Hide ▴
Evidence considered
- REVEL: skipped (no coords)
- BayesDel: skipped (no coords)
- SpliceAI: max_delta=null
- HCI prior: skipped (no gene)
Still missing
- REVEL score
- BayesDel score
- SpliceAI delta scores
- Multiple in silico algorithms supporting a deleterious effect
BP4 No in silico scores available: REVEL, BayesDel, and SpliceAI all failed or were skipped because genomic coordinates and gene could not be resolved. Details ▾Hide ▴
Evidence considered
- REVEL: skipped
- BayesDel: skipped
- SpliceAI: no data
Still missing
- Multiple in silico algorithms supporting a benign effect
BP7 N/AThis is a substitution variant that is highly unlikely to be synonymous and lacks splice prediction data; BP7 is reserved for synonymous (silent) variants with no predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.