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LYFE SCIENCES
Project: HERA
NM_000314.8:c.955_956dup
p.Thr321Ter  ·  PTEN
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Classification rationale
1

The PTEN c.955_956dup (p.Thr321Ter; p.T321*) variant has not been observed in somatic cancers in COSMIC, has not been reported in ClinVar, and is listed by OncoKB as Likely Oncogenic with a likely loss-of-function effect.

clinvar ↗ oncokb ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PTEN PM2 at Supporting strength.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

PTEN-specific null-variant guidance supports PVS1 at Very Strong strength because this duplication introduces a premature termination codon at p.Thr321, which is upstream of the PTEN p.D375 (c.1121) NMD cutoff in transcript NM_000314.8.

cspec ↗
4

SpliceAI predicts no significant splice effect for NM_000314.8:c.955_956dup (max delta score 0.01), and the residue is outside the PTEN PM1 catalytic motifs with no Cancer Hotspots signal at T321.

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 classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer hotspots evidence
06
Cancer hotspots
No cancer hotspot summary recorded.