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LYFE SCIENCES
Project: HERA
NM_000314.8:c.434T>G
p.Phe145Cys  ·  PTEN
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Classification rationale
1

The PTEN c.434T>G (p.Phe145Cys; p.F145C) variant has been observed once in somatic cancers in COSMIC and has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, which is below the PTEN PM2 threshold of 0.001% and supports PM2 at Supporting strength.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

In the PTEN saturation mutagenesis phosphatase assay, p.Phe145Cys had a cumulative activity score of -0.669, which is above the PTEN PS3_Moderate cutoff of <= -1.11 and below the BS3 threshold of >0, so the current functional evidence does not independently meet PS3 or BS3.

cspec ↗
4

Computational evidence supports a deleterious protein effect because the REVEL score is 0.861, above the PTEN PP3 threshold of >0.7, while SpliceAI predicts no significant splice effect with a maximum delta score of 0.01.

cspec ↗ 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 is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: PTEN, a lipid and protein phosphatase, is one of the most frequently mutated genes in cancer.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.861. BayesDel score = 0.334659.
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; COSV100909311, n = 1 times).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueF145
Hotspots ↗