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LYFE SCIENCES
Project: HERA
NM_001202543.1:c.1227G>A
p.Ala409=  ·  CUX1
ACMG/AMP
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Classification rationale
1

The CUX1 NM_001202543.1:c.1227G>A (NP_001189472.1:p.(Ala409=)) variant has not been reported in ClinVar, and curated cancer review resources did not provide variant-specific oncogenic evidence.

clinvar ↗ oncokb ↗
2

This variant is very rare in population databases, with allele frequencies of 8.17e-06 (2/244722; 0.00082%) in gnomAD v2.1 and 8.07e-06 (13/1611678; 0.00081%) in gnomAD v4.1.

gnomad_v2 ↗ gnomad_v4 ↗
3

CUX1 loss of function is an established germline disease mechanism, but this synonymous variant is not a generic PVS1-eligible loss-of-function variant.

pvs1_generic_framework ↗
4

Computational splice prediction does not support a damaging effect, as SpliceAI predicts no significant splice impact with a maximum delta score of 0.00.

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
—
—
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 v2.1This variant is present in gnomAD v2.1 (AF= 8.17254e-06; MAF= 0.00082%, 2/244722 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.36618e-05; MAF= 0.00637%, 1/15708 alleles, homozygotes = 0).
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 8.06613e-06; MAF= 0.00081%, 13/1611678 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 1.3344e-05; MAF= 0.00133%, 1/74940 alleles, homozygotes = 0); grpmax FAF= 5.43e-06.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant is absent from ClinVar.
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie 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 does not lie in a statistically significant hotspot.
ResidueA409
Hotspots ↗