TP53 c.-29+94T>G, p.?
NM_000546.6:c.-29+94T>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.-29+94T>G
Protein Change
?
Location
Exon 1
(Exon 1 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 -29+94t>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: 1.78
VCEP Guidelines
Applied ACMG/AMP Criteria
VCEP Guidelines
PVS1
PVS1 (Not Applied)
Strength Modified
According to VCEP guidelines, PVS1 applies to null variants (nonsense, frameshift, canonical ±1,2 splice) predicted to undergo NMD in TP53. The c.-29+94T>G variant is a deep intronic change outside canonical splice sites and does not create a null allele. Therefore, PVS1 is not applied.
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. c.-29+94T>G does not alter the amino acid sequence and no equivalent pathogenic variant exists. Therefore, PS1 is not applied.
PS2
PS2 (Not Applied)
Strength Modified
According to VCEP guidelines, PS2 applies to confirmed de novo variants with point thresholds. No de novo data are available for c.-29+94T>G. Therefore, PS2 is not applied.
PS3
PS3 (Not Applied)
Strength Modified
According to VCEP guidelines, PS3 requires functional assay evidence of loss of function. No functional data exist for c.-29+94T>G. Therefore, PS3 is not applied.
PS4
PS4 (Not Applied)
Strength Modified
According to VCEP guidelines, PS4 requires proband data meeting point thresholds. There are no reported cases for c.-29+94T>G. Therefore, PS4 is not applied.
PM1
PM1 (Not Applied)
Strength Modified
According to VCEP guidelines, PM1 applies to missense variants within TP53 hotspots. c.-29+94T>G is intronic and not within a protein hotspot. Therefore, PM1 is not applied.
PM2
PM2 (Supporting)
Strength Modified
According to VCEP guidelines, PM2_Supporting applies if allele frequency is <0.00003 in gnomAD. c.-29+94T>G is absent from gnomAD (MAF=0%). Therefore, PM2 is applied at Supporting strength.
PM3
PM3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PM3 applies to variants observed in trans with a pathogenic variant in recessive disorders. No such data exist for TP53 c.-29+94T>G. Therefore, PM3 is not applied.
PM4
PM4 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PM4 applies to protein length changes. c.-29+94T>G does not alter protein length. Therefore, PM4 is not applied.
PM5
PM5 (Not Applied)
Strength Modified
According to VCEP guidelines, PM5 applies to novel missense at residues with known pathogenic missense. c.-29+94T>G is intronic. Therefore, PM5 is not applied.
PM6
PM6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PM6 applies to assumed de novo without confirmation. No de novo information is available for c.-29+94T>G. Therefore, PM6 is not applied.
PP1
PP1 (Not Applied)
Strength Modified
According to VCEP guidelines, PP1 requires segregation in affected family members. No segregation data exist for c.-29+94T>G. Therefore, PP1 is not applied.
PP2
PP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP2 applies to missense variants in genes with low benign missense rates. c.-29+94T>G is intronic. Therefore, PP2 is not applied.
PP3
PP3 (Not Applied)
Strength Modified
According to VCEP guidelines, PP3 requires computational evidence of deleterious impact. SpliceAI score=0 and other in silico predictors are benign, so PP3 is not met. Therefore, PP3 is not applied.
PP4
PP4 (Not Applied)
Strength Modified
According to VCEP guidelines, PP4 requires a specific phenotype match. No phenotype data are available for c.-29+94T>G. Therefore, PP4 is not applied.
PP5
PP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, PP5 applies to variants classified as pathogenic by a reputable source. c.-29+94T>G is not in ClinVar. Therefore, PP5 is not applied.
BA1
BA1 (Not Applied)
Strength Modified
According to VCEP guidelines, BA1 applies if allele frequency ≥0.001. c.-29+94T>G has MAF=0%. Therefore, BA1 is not applied.
BS1
BS1 (Not Applied)
Strength Modified
According to VCEP guidelines, BS1 applies if filtering allele frequency ≥0.0003. c.-29+94T>G is absent from gnomAD. Therefore, BS1 is not applied.
BS2
BS2 (Not Applied)
Strength Modified
According to VCEP guidelines, BS2 requires observation in ≥2 healthy older individuals. No such data exist for c.-29+94T>G. Therefore, BS2 is not applied.
BS3
BS3 (Not Applied)
Strength Modified
According to VCEP guidelines, BS3 requires functional assay evidence of no loss of function. No functional data exist for c.-29+94T>G. Therefore, BS3 is not applied.
BS4
BS4 (Not Applied)
Strength Modified
According to VCEP guidelines, BS4 requires lack of segregation in affected family members. No segregation data exist for c.-29+94T>G. Therefore, BS4 is not applied.
BP1
BP1 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP1 applies to missense in genes where truncating variants cause disease. c.-29+94T>G is intronic. Therefore, BP1 is not applied.
BP2
BP2 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP2 applies when a variant is observed in trans with a pathogenic variant in a dominant gene. No such data exist for c.-29+94T>G. Therefore, BP2 is not applied.
BP3
BP3 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP3 applies to in-frame indels in repetitive regions. c.-29+94T>G is a single nucleotide variant in an intron. Therefore, BP3 is not applied.
BP4
BP4 (Supporting)
According to standard ACMG guidelines, BP4 applies when multiple computational tools predict no impact. SpliceAI=0, CADD=1.78, and other in silico predictors are benign. Therefore, BP4 is applied at Supporting strength.
BP5
BP5 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP5 applies when a variant is reported in a gene with an alternate molecular basis for the phenotype. Not relevant for c.-29+94T>G. Therefore, BP5 is not applied.
BP6
BP6 (Not Applied)
Strength Modified
According to standard ACMG guidelines, BP6 applies when a variant is reported as benign by a reputable source. c.-29+94T>G is not in ClinVar. Therefore, BP6 is not applied.
BP7
BP7 (Supporting)
According to VCEP guidelines, BP7_Supporting applies to intronic variants at or beyond +7 positions with SpliceAI≤0.1. c.-29+94T>G is at +94 and SpliceAI=0. Therefore, BP7 is applied at Supporting strength.