Starting
Initialising…
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Final classification
VUS
c.370C>T

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.

Gene
N/A
Transcript
N/A
HGVS · transcript:coding
NM_000546.6:c.370C>T
Consequence
N/A
GRCh38
N/A
GRCh37
N/A
Basis 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. ▾
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.
Classification rationale
VUS
c.370C>T

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.

Applied criteria · 0 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      —
      Research & evidence
      Population frequency
      v4.1
      This variant is absent from gnomAD v4.1.
      v2.1
      This variant is absent from gnomAD v2.1.
      🇨🇦 CA
      This variant is absent from gnomAD-Canada.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD Canada 🇨🇦
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD 🇨🇦 ↗
      ClinVar No data
      No ClinVar submissions were recorded for this variant.
      In silico No data
      No in-silico prediction was recorded for this variant.
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      Sources & reference links

      No sources recorded.