Genetic Information

Gene & Transcript Details

Gene
TP53
Transcript
NM_000546.5 MANE Select
Total Exons
—
Reference Sequence
NC_000017.10
Alternative Transcripts
IDStatusDetails
NM_000546.3 Alternative 2640 nt | 252–1433
NM_000546.5 RefSeq Select 2591 nt | 203–1384
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

HGVS Notation
NM_000546.5:c.761T>C
Protein Change
I254T
Location
Exon 7 (Exon 7 of )
7
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.0 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Unknown
0 publications
Clinical Statement

""

COSMIC Somatic Evidence

Open
COSMIC ID
COSM44058
Recurrence
9 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC Preview
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Functional Impact & Domains

Functional Domain

Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene TP53.

Functional Studies & Therapeutic Relevance

Functional Summary

Error in OpenAI Consolidation. OncoKB: TP53I254TTP53I254TSomaticNCBI Gene:7157|Show additional gene information Variant OverviewTP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.The TP53 I254T mutation is known to be oncogenic.Hide mutation effect description The TP53 I254T mutation is located in the protein's DNA binding domain. In vitro studies have demonstrated that this mutation is likely inactivating, as evidenced by the loss of p53-mediated transactivation and increased colony formation in the mutant compared to wildtype (PMID: 25584008). JAX-CKB: TP53 I254T lies within the DNA-binding domain of the Tp53 protein (PMID: 15510160). I254T results in decreased Tp53 transactivation activity and reduced ability to suppress colony formation in cell culture (PMID: 25584008).

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

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Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 41 bp
- Donor Loss (DL) 0.0 -21 bp
+ Acceptor Gain (AG) 0.0 -389 bp
+ Donor Gain (DG) 0.0 -311 bp
High impact (≥0.5) Medium impact (0.2-0.49) Low impact (<0.2)

VCEP Guidelines

Applied ACMG/AMP Criteria (VCEP Specific)

Filter Criteria:
PS3

PS3 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

PM2

PM2 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)

BP4

BP4 (Unknown (Pre-LLM))

From pre-LLM assessment (LLM Failed)