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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.144C>A (p.Asp48Glu)

CA000055

141056 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: a73c7ac4-5d9a-4c83-8aab-e4fea34cea32

HGVS expressions

NM_000546.5:c.144C>A
NM_000546.5(TP53):c.144C>A (p.Asp48Glu)
NM_001126112.2:c.144C>A
NM_001126113.2:c.144C>A
NM_001126114.2:c.144C>A
NM_001126118.1:c.27C>A
NM_001276695.1:c.27C>A
NM_001276696.1:c.27C>A
NM_001276760.1:c.27C>A
NM_001276761.1:c.27C>A
NM_001276695.2:c.27C>A
NM_001276696.2:c.27C>A
NM_001276760.2:c.27C>A
NM_001276761.2:c.27C>A
ENST00000269305.8:c.144C>A
ENST00000359597.8:n.144C>A
ENST00000413465.6:n.144C>A
ENST00000420246.6:c.144C>A
ENST00000445888.6:c.144C>A
ENST00000455263.6:c.144C>A
ENST00000503591.1:c.144C>A
ENST00000505014.5:n.400C>A
ENST00000508793.5:c.144C>A
ENST00000509690.5:c.-21-989C>A
ENST00000514944.5:c.96+157C>A
ENST00000604348.5:c.144C>A
ENST00000610292.4:c.27C>A
ENST00000610538.4:c.27C>A
ENST00000615910.4:n.144C>A
ENST00000617185.4:c.144C>A
ENST00000619485.4:c.27C>A
ENST00000620739.4:c.27C>A
ENST00000622645.4:c.27C>A
ENST00000635293.1:c.27C>A
NC_000017.11:g.7676225G>T
CM000679.2:g.7676225G>T
NC_000017.10:g.7579543G>T
CM000679.1:g.7579543G>T
NC_000017.9:g.7520268G>T
NG_017013.2:g.16326C>A

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
BS3 BP4 PM2_Supporting
Not Met criteria codes 14
BS2 BS1 BS4 BP2 PS1 PS3 PS4 PS2 BA1 PP3 PP1 PM6 PM5 PM1

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
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). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, TP53 c.144C>A (p.Asp48Glu) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, PM2_Supporting.
Met criteria codes
BS3
Functional in Kato - all 8 RE show at least 75% of wt transactivation; Giacomelli - Nutlin3 = -0.17, Etoposide = 0.79 Both fall in the retained function category.
PubMed:30224644
PubMed:12826609
PubMed:29979965
BP4
BayesDel is -0.22 and aGVGD is C0
PM2_Supporting
Not Present in gnomAD
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Not Present in gnomAD
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Not Present in gnomAD
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2020-09-04
Published on: 2020-09-04
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