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LYFE SCIENCES
Project: HERA
NM_000314.8:c.253+5G>A
p.?  ·  PTEN
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Classification rationale
1

An RNA study has shown that NM_000314.8:c.253+5G>A causes exon 4 skipping, resulting in the predicted frameshift transcript consequence p.(Ala72Thrfs*5).

PMID:28677221 ↗
2

Under the PTEN-specific PVS1 decision tree, a splice alteration that disrupts the reading frame in biologically relevant transcript NM_000314.8 and lies 5′ to p.D375 (c.1121) meets PVS1 at very strong strength; exon 4 skipping to p.(Ala72Thrfs*5) is consistent with this rule.

3

The variant is absent from gnomAD v2.1 and is observed at 0/1,448,024 alleles in gnomAD v4.1, with 0/33,128 alleles in the highest observed subpopulation, which is below the PTEN PM2 thresholds of 0.001% overall and 0.002% within any subpopulation and supports PM2_Supporting.

gnomad_v4 ↗
4

With PVS1 and PM2_Supporting under the PTEN VCEP framework, NM_000314.8:c.253+5G>A is classified as likely pathogenic.

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
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1Absent from gnomAD v2.1.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1448024 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/33128 alleles, homozygotes = 0).
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.81).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV64300202, n = 2 times).
06
Cancer hotspots
No cancer hotspot summary recorded.