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LYFE SCIENCES
Project: HERA
NM_000546.6:c.267del
p.Ser90ProfsTer33  ·  TP53
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Classification rationale
1

The TP53 c.267del (p.Ser90ProfsTer33) variant has been observed in somatic cancers in COSMIC (30 occurrences) and has been reported in ClinVar with Pathogenic and Likely pathogenic germline submissions.

clinvar ↗
2

This variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, placing its allele frequency below the TP53 PM2 threshold of less than 0.00003.

gnomad_v2 ↗ gnomad_v4 ↗ gnomad_canada ↗ cspec ↗
3

This early frameshift creates a premature stop at codon 122, which is well upstream of the TP53 VCEP p.Lys351 cutoff for predicted nonsense-mediated decay and supports PVS1 at very strong strength.

cspec ↗
4

SpliceAI predicts no significant splice impact for this variant (max delta score 0.07), and this does not weaken the TP53 null-variant interpretation.

spliceai ↗
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
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Pathogenic (2 clinical laboratories) and as Likely pathogenic (1 clinical laboratory). (ClinVarID = 156515)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.07).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52685476, n = 30 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueS90
Hotspots ↗