Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000546.5(TP53):c.372C>A (p.Cys124Ter)

CA397844214

458537 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a9d7558a-f941-4cec-95c8-682dafc6ca40
Approved on: 2024-08-05
Published on: 2024-08-05

HGVS expressions

NM_000546.5:c.372C>A
NM_000546.5(TP53):c.372C>A (p.Cys124Ter)
NC_000017.11:g.7675997G>T
CM000679.2:g.7675997G>T
NC_000017.10:g.7579315G>T
CM000679.1:g.7579315G>T
NC_000017.9:g.7520040G>T
NG_017013.2:g.16554C>A
ENST00000503591.2:c.372C>A
ENST00000508793.6:c.372C>A
ENST00000509690.6:c.-21-761C>A
ENST00000514944.6:c.96+385C>A
ENST00000604348.6:c.372C>A
ENST00000269305.9:c.372C>A
ENST00000269305.8:c.372C>A
ENST00000359597.8:c.372C>A
ENST00000413465.6:c.372C>A
ENST00000420246.6:c.372C>A
ENST00000445888.6:c.372C>A
ENST00000455263.6:c.372C>A
ENST00000503591.1:c.372C>A
ENST00000505014.5:n.628C>A
ENST00000508793.5:c.372C>A
ENST00000509690.5:c.-21-761C>A
ENST00000514944.5:c.96+385C>A
ENST00000604348.5:c.372C>A
ENST00000610292.4:c.255C>A
ENST00000610538.4:c.255C>A
ENST00000615910.4:c.340+28C>A
ENST00000617185.4:c.372C>A
ENST00000619485.4:c.255C>A
ENST00000620739.4:c.255C>A
ENST00000622645.4:c.255C>A
ENST00000635293.1:c.255C>A
NM_001126112.2:c.372C>A
NM_001126113.2:c.372C>A
NM_001126114.2:c.372C>A
NM_001126118.1:c.255C>A
NM_001276695.1:c.255C>A
NM_001276696.1:c.255C>A
NM_001276760.1:c.255C>A
NM_001276761.1:c.255C>A
NM_001276695.2:c.255C>A
NM_001276696.2:c.255C>A
NM_001276760.2:c.255C>A
NM_001276761.2:c.255C>A
NM_000546.6:c.372C>A
NM_001126112.3:c.372C>A
NM_001126113.3:c.372C>A
NM_001126114.3:c.372C>A
NM_001126118.2:c.255C>A
NM_001276695.3:c.255C>A
NM_001276696.3:c.255C>A
NM_001276760.3:c.255C>A
NM_001276761.3:c.255C>A
More

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PS2
Not Met criteria codes 6
PM1 PM6 BS3 PS3 PS4 PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6 c.372C>A (p.Cys124Ter) is a TP53 nonsense variant upstream of p.Lys351. The variant is predicted to undergo nonsense-mediated decay (PVS1; PMID: 22233476). This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 2 individuals with LFS-associated cancers totaling 4 phenotype points (PS2; PMID: 22233476, 32658383). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for Li Fraumeni Syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PVS1, PS2, PM2_Supporting. (Bayesian Points: 13; VCEP specifications version 2.0; 7/24/2024).
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PVS1
The NM_000546.6 c.372C>A (p.Cys124Ter) is a TP53 nonsense variant upstream of p.Lys351. The variant is predicted to undergo nonsense-mediated decay (PVS1; PMID: 22233476).
PS2
This variant has been identified as a de novo occurrence with unconfirmed parental relationships in 2 individual(s) with an LFS-associated cancer totaling 4 phenotype points (PS2; PMID: 22233476, 32658383).
Not Met criteria codes
PM1
This variant does not reside within a region of TP53 that is defined as a mutational hotspot or critical functional domain by the ClinGen TP53 VCEP (PM1 not met).
PM6
This evidence code is not currently applicable for TP53 VCEP curations.
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
This variant received a total of 1 point across 2 unrelated probands. However, PS4 cannot be applied because individuals are counted towards de novo code PS2. (PS4 not met; PMIDs: 22233476, 32658383).
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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