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]
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.847C>T (p.Arg283Cys)

CA000457

127824 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0b9a7a17-b7b8-4223-bd64-69617a2d691d
Approved on: 2019-09-16
Published on: 2020-01-24

HGVS expressions

NM_000546.5:c.847C>T
NM_000546.5(TP53):c.847C>T (p.Arg283Cys)
NC_000017.11:g.7673773G>A
CM000679.2:g.7673773G>A
NC_000017.10:g.7577091G>A
CM000679.1:g.7577091G>A
NC_000017.9:g.7517816G>A
NG_017013.2:g.18778C>T
ENST00000503591.2:c.847C>T
ENST00000508793.6:c.847C>T
ENST00000509690.6:c.451C>T
ENST00000514944.6:c.568C>T
ENST00000604348.6:c.826C>T
ENST00000269305.9:c.847C>T
ENST00000269305.8:c.847C>T
ENST00000359597.8:c.847C>T
ENST00000413465.6:c.782+408C>T
ENST00000420246.6:c.847C>T
ENST00000445888.6:c.847C>T
ENST00000455263.6:c.847C>T
ENST00000504290.5:c.451C>T
ENST00000504937.5:c.451C>T
ENST00000509690.5:c.451C>T
ENST00000510385.5:c.451C>T
ENST00000610292.4:c.730C>T
ENST00000610538.4:c.730C>T
ENST00000610623.4:c.370C>T
ENST00000615910.4:c.814C>T
ENST00000617185.4:c.847C>T
ENST00000618944.4:c.370C>T
ENST00000619186.4:c.370C>T
ENST00000619485.4:c.730C>T
ENST00000620739.4:c.730C>T
ENST00000622645.4:c.730C>T
ENST00000635293.1:c.730C>T
NM_001126112.2:c.847C>T
NM_001126113.2:c.847C>T
NM_001126114.2:c.847C>T
NM_001126115.1:c.451C>T
NM_001126116.1:c.451C>T
NM_001126117.1:c.451C>T
NM_001126118.1:c.730C>T
NM_001276695.1:c.730C>T
NM_001276696.1:c.730C>T
NM_001276697.1:c.370C>T
NM_001276698.1:c.370C>T
NM_001276699.1:c.370C>T
NM_001276760.1:c.730C>T
NM_001276761.1:c.730C>T
NM_001276695.2:c.730C>T
NM_001276696.2:c.730C>T
NM_001276697.2:c.370C>T
NM_001276698.2:c.370C>T
NM_001276699.2:c.370C>T
NM_001276760.2:c.730C>T
NM_001276761.2:c.730C>T
NM_000546.6:c.847C>T
NM_001126112.3:c.847C>T
NM_001126113.3:c.847C>T
NM_001126114.3:c.847C>T
NM_001126115.2:c.451C>T
NM_001126116.2:c.451C>T
NM_001126117.2:c.451C>T
NM_001126118.2:c.730C>T
NM_001276695.3:c.730C>T
NM_001276696.3:c.730C>T
NM_001276697.3:c.370C>T
NM_001276698.3:c.370C>T
NM_001276699.3:c.370C>T
NM_001276760.3:c.730C>T
NM_001276761.3:c.730C>T
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Uncertain Significance

Met criteria codes 2
PP3 BS3
Not Met criteria codes 1
BP5

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 15 or higher (PP3). However, transactivation assays show retained function according to Kato, et al. and there is no evidence of a dominant negative effect or loss of function according to Giacomelli, et al. (BS3; PMID: 12826609, 30224644). In summary, the clinical significance of TP53 c.847C>T; p.Arg283Cys is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PP3 and BS3.
Met criteria codes
PP3
BayesDel suggests pathogenic & AGVGD = Class C55
BS3
Transactivation assay shows retained function and there is no dominant negative effects or evidence of LOF in Giacomelli data
No dominant negative effects or evidence of LOF PubMed:30224644
Transactivation assay shows retained function PubMed:12826609
Not Met criteria codes
BP5
This variant was found in one woman with breast cancer at 29 and ovarian cancer at 56 who also had a pathogenic variant in BRCA2, but this does not rule out the pathogencity of this variant.
Curation History
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