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LYFE SCIENCES
Project: HERA
NM_000314.8:c.322C>G
p.Leu108Val  ·  PTEN
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Legacy Engine
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Classification rationale
1

The PTEN c.322C>G (p.Leu108Val) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

clinvar ↗
2

This variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, which supports rarity below the PTEN PM2 threshold of 0.001%.

gnomad_v2 ↗ gnomad_v4 ↗ gnomad_canada ↗ cspec ↗
3

In the PTEN saturation mutagenesis phosphatase assay accepted by the PTEN Expert Panel, p.Leu108Val had a high-confidence cumulative fitness score of 1.160568514, which is above the BS3 threshold of >0 and well above the PS3_Moderate damaging threshold of ≤-1.11, supporting no damaging effect on protein function.

cspec ↗
4

Computational evidence is indeterminate overall: REVEL is 0.514, which is between the PTEN BP4 cutoff of <0.5 and PP3 cutoff of >0.7; BayesDel is 0.180271; and SpliceAI predicts no splice impact with a maximum delta score of 0.00.

spliceai ↗ cspec ↗
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: Likely Oncogenic
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. 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 = 0.00). REVEL score = 0.514. BayesDel score = 0.180271.
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant lies in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant lies in a statistically significant hotspot.
ResidueL108
Hotspots ↗