Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_000546.5 | RefSeq Select | 2591 nt | 203–1384 |
| NM_000546.3 | Alternative | 2640 nt | 252–1433 |
| NM_000546.6 | MANE Select | 2512 nt | 143–1324 |
| NM_000546.4 | Alternative | 2586 nt | 198–1379 |
| NM_000546.2 | Alternative | 2629 nt | 252–1433 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -286 bp |
| Donor Loss (DL) | 0.0 | 202 bp |
| Acceptor Gain (AG) | 0.0 | -2 bp |
| Donor Gain (DG) | 0.0 | -2 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to VCEP guidelines, 'Canonical splice variants (±1,2 intronic positions): PVS1 applies to predicted splicing alterations...' The variant c.-29+121G>T is located at +121 relative to the exon, outside the canonical ±1,2 splice sites. Therefore, PVS1 is not applied.
PS1 (Not Applied)
According to VCEP guidelines, PS1 applies when a variant results in the same amino acid change as a previously established pathogenic variant. This deep intronic variant has no protein change. Therefore, PS1 is not applied.
PS2 (Not Applied)
According to VCEP guidelines, PS2 requires a confirmed de novo occurrence (maternity and paternity confirmed). No de novo data are available for this variant. Therefore, PS2 is not applied.
PS3 (Not Applied)
According to VCEP guidelines, PS3 requires well-established functional studies showing loss of function in TP53-specific assays. No functional studies have been performed for this variant. Therefore, PS3 is not applied.
PS4 (Not Applied)
According to VCEP guidelines, PS4 requires case–control or proband count evidence with defined point thresholds. No case data are available. Therefore, PS4 is not applied.
PM1 (Not Applied)
According to VCEP guidelines, PM1 applies to missense variants in TP53 hotspots (codons 175,245,248,249,273,282) or recurrent somatic hotspots. This intronic variant does not affect a hotspot codon. Therefore, PM1 is not applied.
PM2 (Supporting)
According to VCEP guidelines, 'PM2 applies at Supporting strength for TP53 if allele frequency <0.00003 in gnomAD.' The variant is absent from gnomAD (MAF=0%). Therefore, PM2 is applied at Supporting strength.
PM3 (Not Applied)
According to standard ACMG guidelines, PM3 applies to detected in trans observations in a recessive disorder. TP53 is not recessive and no trans data exist. Therefore, PM3 is not applied.
PM4 (Not Applied)
According to standard ACMG guidelines, PM4 applies to protein length changes such as in-frame indels. This is an intronic variant not affecting coding sequence. Therefore, PM4 is not applied.
PM5 (Not Applied)
According to VCEP guidelines, PM5 applies to novel missense changes at residues with established pathogenic missense variants. This is noncoding. Therefore, PM5 is not applied.
PM6 (Not Applied)
According to VCEP guidelines, PM6 applies to presumed de novo without confirmation. No de novo evidence is available. Therefore, PM6 is not applied.
PP1 (Not Applied)
According to VCEP guidelines, PP1 requires segregation data across affected family members. No segregation data are available. Therefore, PP1 is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, PP2 applies to missense variants in genes with low benign missense variation rate. This is an intronic variant. Therefore, PP2 is not applied.
PP3 (Not Applied)
According to VCEP guidelines, PP3 applies to missense or splice region variants with in silico evidence of impact (SpliceAI ≥0.2). SpliceAI predicts no impact (score=0). Therefore, PP3 is not applied.
PP4 (Not Applied)
According to VCEP guidelines, PP4 relates to somatic VAF observations. This is a germline assessment with no somatic data. Therefore, PP4 is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, PP5 applies when a reputable source classifies a variant as pathogenic. No such classification exists for this variant. Therefore, PP5 is not applied.
BA1 (Not Applied)
According to VCEP guidelines, BA1 requires FAF ≥0.001 in a continental subpopulation. The variant is absent (FAF=0%). Therefore, BA1 is not applied.
BS1 (Not Applied)
According to VCEP guidelines, BS1 requires FAF ≥0.0003 but <0.001. The variant is absent. Therefore, BS1 is not applied.
BS2 (Not Applied)
According to VCEP guidelines, BS2 applies when ≥8 healthy older females are observed with the variant. No such observations exist. Therefore, BS2 is not applied.
BS3 (Not Applied)
According to VCEP guidelines, BS3 requires functional evidence of no LOF in TP53 assays. No functional data exist. Therefore, BS3 is not applied.
BS4 (Not Applied)
According to VCEP guidelines, BS4 requires lack of segregation in affected family members. No segregation data exist. Therefore, BS4 is not applied.
BP1 (Not Applied)
According to standard ACMG guidelines, BP1 applies to missense variants in genes where only truncating variants cause disease. This is intronic. Therefore, BP1 is not applied.
BP2 (Not Applied)
According to standard ACMG guidelines, BP2 applies when in cis with a pathogenic variant or in trans for a dominant disorder. No such data. Therefore, BP2 is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, BP3 applies to in-frame indels in repetitive regions. This is a single nucleotide intronic variant. Therefore, BP3 is not applied.
BP4 (Not Applied)
According to VCEP guidelines, BP4 applies to missense variants with benign in silico scores. This is an intronic variant. Therefore, BP4 is not applied.
BP5 (Not Applied)
According to standard ACMG guidelines, BP5 applies when a variant is found in trans with a pathogenic variant for a dominant disorder. No such data. Therefore, BP5 is not applied.
BP6 (Not Applied)
According to standard ACMG guidelines, BP6 applies when a reputable source classifies variant as benign. No such assertion exists. Therefore, BP6 is not applied.
BP7 (Supporting)
According to VCEP guidelines, 'Supporting BP7: an intronic variant at or beyond +7 to -21 positions with SpliceAI ≤0.1 and no predicted splice impact.' c.-29+121G>T is at +121 and SpliceAI=0. Therefore, BP7 is applied at Supporting strength.