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.
26 criteria with recorded statuses: 0 met · 0 not met · 25 not assessed · 1 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
Variant normalization failed: Mutalyzer returned HTTP 422, and VariantValidator reported a ReferenceMismatchError (reference base at NM_000546.6:c.370 is T, not C). The gene, protein consequence, and genomic coordinates could not be resolved.
PVS1 is not applicable — NM_000546.6:c.370C>T is a substitution variant, not a null variant eligible for PVS1 consideration.
All other criteria could not be assessed. Population databases (gnomAD v2.1, v4.1), ClinVar, in silico predictors (REVEL, BayesDel, SpliceAI), functional databases (COSMIC, OncoKB, Hotspots), and the published literature returned no usable evidence for this variant because gene/coordinate lookup prerequisites were not met.
No classification can be assigned. The variant cannot be evaluated under ACMG/AMP 2015 criteria without successful normalization. Manual review is required: confirm the correct HGVS expression (NM_000546.6:c.370C>T may have an incorrect reference base), re-run normalization, and re-attempt all evidence gathering.
No criteria match.
Not assessed · 25 · no assessment recorded
PS1 Cannot assess. Variant normalization failed (Mutalyzer HTTP 422; VariantValidator reports reference base at NM_000546.6:c.370 is T, not C, causing a ReferenceMismatchError). No protein consequence could be determined, and no alternate pathogenic variants at the same residue are available for comparison. Details ▾Hide ▴
Still missing
- Variant normalization failed — protein consequence and residue unknown.
- No ClinVar or literature comparators available.
PS2 Cannot assess. No de novo observations for this variant were found in the literature or clinical databases. No publications were identified for this variant. Details ▾Hide ▴
Still missing
- No de novo data available.
- No publications identified.
- Variant normalization failed
- database lookups incomplete.
PS3 Cannot assess. No functional assay data (well-established in vitro or in vivo studies) were identified for this variant. No publications were retrieved. Details ▾Hide ▴
Still missing
- No functional data available.
- No publications identified.
- Variant normalization failed.
PS4 Cannot assess. No case-control or cohort prevalence data were available. gnomAD v2.1 and v4.1 lookups did not complete, and no publications with affected-individual counts were identified. Details ▾Hide ▴
Still missing
- gnomAD v2.1 and v4.1 queries incomplete.
- No publications with case counts.
- Variant normalization failed.
PM1 Cannot assess. The protein domain and residue position could not be determined due to normalization failure, so location within a mutational hot spot or critical functional domain cannot be confirmed. Details ▾Hide ▴
Still missing
- Protein residue/domain unknown due to normalization failure.
- Hotspots database returned no data.
PM2 Cannot assess. gnomAD v2.1 and v4.1 allele frequency data are unavailable (queries did not complete). gnomAD-Canada v1.0 reports the variant as absent (AC=0, AN=0), but this is a small reference set and cannot substitute for the full gnomAD databases. A definitive PM2 determination cannot be made. Details ▾Hide ▴
Evidence considered
- gnomAD-Canada v1.0: absent (AC=0
- AN=0).
- gnomAD v2.1 and v4.1: data unavailable.
Still missing
- gnomAD v2.1 and v4.1 population data unavailable.
- Variant normalization failed
- gnomAD queries could not be executed.
PM5 Cannot assess. Protein residue context could not be resolved due to normalization failure. The automated PM5 candidate harvesting was unsuccessful — no same-residue comparator variants were identified. Details ▾Hide ▴
Still missing
- Protein residue unknown.
- No PM5 comparator candidates identified.
- Variant normalization failed.
PM6 Cannot assess. No de novo observations (with confirmed maternity and paternity) were identified for this variant in any available source. Details ▾Hide ▴
Still missing
- No de novo data available.
- No publications identified.
- Variant normalization failed.
PP1 Cannot assess. No cosegregation data (family studies showing the variant tracks with disease) were available. Details ▾Hide ▴
Still missing
- No segregation data available.
- No family studies identified.
PP2 Cannot assess. The gene and its missense constraint metrics (z-score, benign missense rate) could not be determined due to normalization failure. PP2 requires a low rate of benign missense variation in the gene. Details ▾Hide ▴
Still missing
- Gene not resolved.
- Missense constraint metrics unavailable.
- Variant normalization failed.
PP3 Cannot assess. In silico predictors (REVEL, BayesDel, SpliceAI) could not be queried because genomic coordinates were not available due to normalization failure. No computational evidence of deleterious effect can be generated. Details ▾Hide ▴
Still missing
- REVEL
- BayesDel
- SpliceAI scores unavailable.
- Genomic coordinates unknown.
- Variant normalization failed.
PP4 Cannot assess. No phenotypic data (patient presentation, family history, disease specificity) were provided or identified for this variant. Details ▾Hide ▴
Still missing
- No phenotypic data available.
PP5 Cannot assess. No reputable source (ClinVar expert panel, clinical laboratory, or published study) has classified this variant as pathogenic. ClinVar lookup was skipped due to normalization failure. Details ▾Hide ▴
Still missing
- ClinVar lookup skipped.
- No expert classification available.
- Variant normalization failed.
BA1 Cannot assess. gnomAD v2.1 and v4.1 allele frequency data are unavailable. BA1 requires an allele frequency >1% in population databases, but the necessary data could not be retrieved. Details ▾Hide ▴
Still missing
- gnomAD allele frequencies unavailable.
- Variant normalization failed.
BS1 Cannot assess. gnomAD v2.1 and v4.1 allele frequency data are unavailable. BS1 requires an allele frequency >0.3% in population databases, but the necessary data could not be retrieved. Details ▾Hide ▴
Still missing
- gnomAD allele frequencies unavailable.
- Variant normalization failed.
BS2 Cannot assess. No observations of this variant in healthy adults (in trans with a pathogenic variant for a fully penetrant dominant disorder, or in a homozygous state) were identified. Details ▾Hide ▴
Still missing
- No population or clinical observation data available.
- Variant normalization failed.
BS3 Cannot assess. No well-established functional studies demonstrating no damaging effect were identified for this variant. Details ▾Hide ▴
Still missing
- No functional benign-effect data available.
- No publications identified.
BS4 Cannot assess. No segregation data demonstrating lack of cosegregation with disease were available. Details ▾Hide ▴
Still missing
- No segregation data available.
BP1 Cannot assess. The gene and its disease mechanism (truncating vs missense) could not be determined due to normalization failure. BP1 requires a gene where primarily truncating variants cause disease. Details ▾Hide ▴
Still missing
- Gene not resolved.
- Variant normalization failed.
BP2 Cannot assess. No observations of this variant in trans with a known pathogenic variant for a fully penetrant dominant disorder were identified. Details ▾Hide ▴
Still missing
- No trans-phase observation data available.
- Variant normalization failed.
BP4 Cannot assess. In silico predictors (REVEL, BayesDel, SpliceAI) could not be queried because genomic coordinates were unavailable due to normalization failure. No computational evidence suggesting a benign effect can be generated. Details ▾Hide ▴
Still missing
- REVEL
- BayesDel
- SpliceAI scores unavailable.
- Genomic coordinates unknown.
- Variant normalization failed.
BP5 Cannot assess. No cases were identified in which this variant was found in an individual with an alternate molecular basis for disease. Details ▾Hide ▴
Still missing
- No alternate molecular basis cases identified.
- Variant normalization failed.
BP6 Cannot assess. No reputable source (ClinVar, clinical laboratory, or published study) has classified this variant as benign. ClinVar lookup was skipped due to normalization failure. Details ▾Hide ▴
Still missing
- ClinVar lookup skipped.
- No benign classification available.
- Variant normalization failed.
BP7 Cannot assess. BP7 applies to synonymous (silent) variants with no predicted splice impact. The protein consequence of NM_000546.6:c.370C>T could not be determined due to normalization failure, so it is unknown whether this substitution is synonymous or missense. Details ▾Hide ▴
Still missing
- Protein consequence unknown.
- Cannot determine if variant is synonymous or missense.
- Variant normalization failed.
PS5 Cannot assess. No ClinVar entry or reputable source classification was found for this variant. ClinVar lookup was skipped due to normalization failure. Details ▾Hide ▴
Still missing
- ClinVar lookup skipped.
- No established pathogenic assertion available.
- Variant normalization failed.
Not applicable · 1· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical splice site, initiation codon, single/multi-exon deletion). NM_000546.6:c.370C>T is a substitution; without evidence of a stop-gain or splice-disrupting consequence, PVS1 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant type is substitution
- not a null variant.
Identifiers
- Coding (HGVS c.)
- NM_000546.6:c.370C>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 Cannot assess. In silico predictors (REVEL, BayesDel, SpliceAI) could not be queried because genomic coordinates were not available due to normalization failure. No computational evidence of deleterious effect can be generated. Details ▾Hide ▴
Still missing
- REVEL
- BayesDel
- SpliceAI scores unavailable.
- Genomic coordinates unknown.
- Variant normalization failed.
BP4 Cannot assess. In silico predictors (REVEL, BayesDel, SpliceAI) could not be queried because genomic coordinates were unavailable due to normalization failure. No computational evidence suggesting a benign effect can be generated. Details ▾Hide ▴
Still missing
- REVEL
- BayesDel
- SpliceAI scores unavailable.
- Genomic coordinates unknown.
- Variant normalization failed.
BP7 Cannot assess. BP7 applies to synonymous (silent) variants with no predicted splice impact. The protein consequence of NM_000546.6:c.370C>T could not be determined due to normalization failure, so it is unknown whether this substitution is synonymous or missense. Details ▾Hide ▴
Still missing
- Protein consequence unknown.
- Cannot determine if variant is synonymous or missense.
- Variant normalization failed.
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.