TP53 c.*9A>G, p.?
NM_000546.6:c.*9A>G
Population Frequency
0.0 in 100,000
Rare
ClinVar Classification
Unknown
0 publications
REVEL Score
N/A
Not Available
COSMIC Recurrence
0 occurrences
No Criteria Applied
Classification Evidence
Detailed Information
Genetic Information
Gene & Transcript Details
Gene
TP53
Transcript
NM_000546.6
MANE Select
Total Exons
11
Strand
Reverse (−)
Reference Sequence
NC_000017.10
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_000546.5 | RefSeq Select | 11 exons | Reverse |
| NM_000546.3 | Alternative | 11 exons | Reverse |
| NM_000546.4 | Alternative | 11 exons | Reverse |
| NM_000546.2 | Alternative | 11 exons | Reverse |
Variant Details
HGVS Notation
NM_000546.6:c.*9A>G
Protein Change
?
Location
Exon 11
(Exon 11 of 11)
5'
Exon Structure (11 total)
3'
Functional Consequence
Loss of Function
Related Variants
Variant interpretation based on transcript NM_000546.6
Clinical Evidence
Population Frequency
Global Frequency
0.0 in 100,000
Extremely Rare
Global: 0.0%
0%
0.0005%
0.001%
0.01%
0.05%
1%+
ACMG Criteria Applied
PM2
This variant is not present in gnomAD (PM2 criteria applies).
Classification
Unknown
Publications
0 publications
Clinical Statement
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Functional Studies
Summary
The TP53 *9a>G variant has not been functionally characterized, and its biological significance remains unknown.
Computational Evidence
Pathogenicity Predictions
Predictor Consensus
Mixed/VUS
PP3 Applied
No
Additional Predictors
Benign:
CADD: 0.03
VCEP Guidelines
Applied ACMG/AMP Criteria
VCEP Guidelines
PVS1
PVS1 (Not Applied)
Strength Modified
According to VCEP guidelines, PVS1 applies to predicted null variants (nonsense, frameshift, canonical ±1,2 splice, initiation codon) in TP53 where loss-of-function is a known mechanism of disease. The evidence for this variant shows: c.*9A>G is a 3′ UTR change, not predicted to introduce a PTC or disrupt splicing at canonical sites. Therefore, this criterion is not applied because the variant is noncoding and does not meet PVS1 definitions.
PS1
PS1 (Not Applied)
Strength Modified
According to VCEP guidelines, PS1 applies when a variant results in the same amino acid change as a previously established pathogenic variant. The evidence for this variant shows: c.*9A>G is noncoding and does not alter an amino acid. Therefore, this criterion is not applied because there is no amino acid change.
PS2
PS2 (Not Applied)
Strength Modified
According to VCEP guidelines, PS2 applies for confirmed de novo variants with points-based strength. The evidence for this variant shows: no de novo segregation or parental testing information is available. Therefore, this criterion is not applied due to lack of de novo evidence.
PS3
PS3 (Not Applied)
Strength Modified
According to VCEP guidelines, PS3 requires functional assay data demonstrating a deleterious effect on TP53 function. The evidence for this variant shows: no functional studies have been performed. Therefore, this criterion is not applied because functional data are missing.
PS4
PS4 (Not Applied)
Strength Modified
According to VCEP guidelines, PS4 applies when there is an increased prevalence of the variant in affected individuals meeting point thresholds. The evidence for this variant shows: no case-control or proband data are available. Therefore, this criterion is not applied due to lack of case evidence.
PM1
PM1 (Not Applied)
Strength Modified
According to VCEP guidelines, PM1 applies to missense variants in specified TP53 hotspots or cancer hotspots. The evidence for this variant shows: c.*9A>G is noncoding and outside the DNA-binding domain. Therefore, this criterion is not applied because the variant is not a missense in a hotspot.
PM2
PM2 (Supporting)
Strength Modified
According to VCEP guidelines, the rule for PM2 is: "This rule should be applied at supporting level. Variant should have an allele frequency of less than 0.00003 (0.003%) in gnomAD or another large sequenced population." The evidence for this variant shows: c.*9A>G is absent from gnomAD (allele frequency 0%). Therefore, this criterion is applied at Supporting strength because the variant meets the population frequency threshold.
PM3
PM3 (Not Applied)
Strength Modified
According to VCEP guidelines, PM3 applies to variants detected in trans with a pathogenic variant for recessive disorders. The evidence for this variant shows: not assessed in a recessive context and no in trans data available. Therefore, this criterion is not applied.
PM4
PM4 (Not Applied)
Strength Modified
According to VCEP guidelines, PM4 applies to protein length–altering variants (in-frame indels, stop-loss). The evidence for this variant shows: c.*9A>G is a UTR variant with no impact on protein length. Therefore, this criterion is not applied.
PM5
PM5 (Not Applied)
Strength Modified
According to VCEP guidelines, PM5 applies to novel missense changes at residues with established pathogenic missense variants. The evidence for this variant shows: c.*9A>G is noncoding. Therefore, this criterion is not applied.
PM6
PM6 (Not Applied)
Strength Modified
According to VCEP guidelines, PM6 applies to presumed de novo variants without confirmation. The evidence for this variant shows: no de novo or parental information. Therefore, this criterion is not applied.
PP1
PP1 (Not Applied)
Strength Modified
According to VCEP guidelines, PP1 applies for cosegregation in families with LFS-associated cancers. The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
PP2
PP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP2 applies to missense variants in a gene with a low rate of benign missense variation. The evidence for this variant shows: it is noncoding. Therefore, this criterion is not applied.
PP3
PP3 (Not Applied)
Strength Modified
According to VCEP guidelines, PP3 applies to deleterious computational predictions (e.g., BayesDel ≥0.16 for missense or SpliceAI ≥0.2). The evidence for this variant shows: SpliceAI predicts 0.03 (below thresholds) and BayesDel not applicable. Therefore, this criterion is not applied.
PP4
PP4 (Not Applied)
Strength Modified
According to VCEP guidelines, PP4 applies to specific tumour allele fraction observations. The evidence for this variant shows: no tumour or phenotype data. Therefore, this criterion is not applied.
PP5
PP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP5 applies to variants asserted pathogenic by reputable sources. The evidence for this variant shows: no entries in ClinVar or other expert sources. Therefore, this criterion is not applied.
BA1
BA1 (Not Applied)
Strength Modified
According to VCEP guidelines, BA1 applies for filtering allele frequency ≥0.001 in gnomAD. The evidence for this variant shows: allele frequency 0%. Therefore, this criterion is not applied.
BS1
BS1 (Not Applied)
Strength Modified
According to VCEP guidelines, BS1 applies for filtering allele frequency ≥0.0003 but <0.001. The evidence for this variant shows: allele frequency 0%. Therefore, this criterion is not applied.
BS2
BS2 (Not Applied)
Strength Modified
According to VCEP guidelines, BS2 applies when ≥8 unrelated healthy females ≥60 years without cancer carry the variant. The evidence for this variant shows: no healthy adult data. Therefore, this criterion is not applied.
BS3
BS3 (Not Applied)
Strength Modified
According to VCEP guidelines, BS3 applies to functional assays showing no loss of function. The evidence for this variant shows: no functional assay data. Therefore, this criterion is not applied.
BS4
BS4 (Not Applied)
Strength Modified
According to VCEP guidelines, BS4 applies to lack of segregation in affected family members. The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
BP1
BP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP1 applies to missense variants in genes where only truncating variants cause disease. The evidence for this variant shows: noncoding UTR change. Therefore, this criterion is not applied.
BP2
BP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP2 applies when a variant is observed in cis or trans with a pathogenic variant affecting interpretation. The evidence for this variant shows: no such observations. Therefore, this criterion is not applied.
BP3
BP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP3 applies to in-frame deletions/insertions in repetitive regions without a known function. The evidence for this variant shows: single nucleotide change in UTR. Therefore, this criterion is not applied.
BP4
BP4 (Supporting)
According to VCEP guidelines, the rule for BP4 Supporting is: "Silent or Intronic Variants (outside ±1,2 positions): SpliceAI ≤ 0.1". The evidence for this variant shows: SpliceAI predicts a maximal score of 0.03, indicating no impact on splicing. Therefore, this criterion is applied at Supporting strength because the variant is noncoding outside splice sites with benign computational predictions.
BP5
BP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP5 applies when a variant is found in a case with an alternate molecular basis for disease. The evidence for this variant shows: no such cases reported. Therefore, this criterion is not applied.
BP6
BP6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP6 applies to well-established benign assertions by reputable sources. The evidence for this variant shows: no such assertions exist. Therefore, this criterion is not applied.
BP7
BP7 (Not Applied)
Strength Modified
According to VCEP guidelines, BP7 applies to synonymous or intronic variants outside ±1,2 positions with no splicing impact. The evidence for this variant shows: c.*9A>G is in the 3′ UTR, not a synonymous codon or intronic position. Therefore, this criterion is not applied.