Back
LYFE SCIENCES
Project: HERA
NM_000546.6:c.370C>T
ACMG/AMP
Starting
Initialising…
0%
Legacy Engine
Processing…
Classification rationale
1

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.

2

PVS1 is not applicable — NM_000546.6:c.370C>T is a substitution variant, not a null variant eligible for PVS1 consideration.

3

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.

4

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
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
Rationale
Select a criterion to inspect its explanation.
Evidence used
Gaps remaining
Rule
Publications
Research and evidence
01
Population
gnomAD v2.1Available
gnomAD v4.1Available
gnomAD CanadaAvailable
02
ClinVar
No ClinVar summary recorded.
03
Functional
No functional summary recorded.
04
In silico
No in silico summary recorded.
05
COSMIC
No COSMIC summary recorded.
06
Cancer hotspots
No cancer hotspot summary recorded.