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.11C>T (p.Pro4Leu)

CA10583686

237941 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 410f531a-d916-4dbc-9751-ea42adb439f2
Approved on: 2021-08-04
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.11C>T
NM_000546.5(TP53):c.11C>T (p.Pro4Leu)
ENST00000269305.9:c.11C>T
ENST00000269305.8:c.11C>T
ENST00000359597.8:n.11C>T
ENST00000413465.6:n.11C>T
ENST00000420246.6:c.11C>T
ENST00000445888.6:c.11C>T
ENST00000455263.6:c.11C>T
ENST00000503591.1:c.11C>T
ENST00000505014.5:n.150C>T
ENST00000508793.5:c.11C>T
ENST00000509690.5:c.-21-1348C>T
ENST00000514944.5:c.11C>T
ENST00000604348.5:c.11C>T
ENST00000610292.4:c.-224C>T
ENST00000610538.4:c.-107C>T
ENST00000615910.4:n.11C>T
ENST00000617185.4:c.11C>T
ENST00000619485.4:c.-107C>T
ENST00000620739.4:c.-107C>T
ENST00000622645.4:c.-107C>T
ENST00000635293.1:c.-107C>T
NM_001126112.2:c.11C>T
NM_001126113.2:c.11C>T
NM_001126114.2:c.11C>T
NM_001126118.1:c.-224C>T
NM_001276695.1:c.-107C>T
NM_001276696.1:c.-107C>T
NM_001276760.1:c.-107C>T
NM_001276761.1:c.-107C>T
NM_001276695.2:c.-107C>T
NM_001276696.2:c.-107C>T
NM_001276760.2:c.-107C>T
NM_001276761.2:c.-107C>T
NM_000546.6:c.11C>T
NM_001126112.3:c.11C>T
NM_001126113.3:c.11C>T
NM_001126114.3:c.11C>T
NM_001126118.2:c.-224C>T
NM_001276695.3:c.-107C>T
NM_001276696.3:c.-107C>T
NM_001276760.3:c.-107C>T
NM_001276761.3:c.-107C>T
NC_000017.11:g.7676584G>A
CM000679.2:g.7676584G>A
NC_000017.10:g.7579902G>A
CM000679.1:g.7579902G>A
NC_000017.9:g.7520627G>A
NG_017013.2:g.15967C>T
More

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
PM2_Supporting BS3 BP4
Not Met criteria codes 14
PS4 PS3 PS1 PP1 PP3 PM1 PM5 BA1 PVS1 BS4 BS1 BS2 BP7 BP2

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). Transactivation assays show [retained/supertransactivation] 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, TP53 c.11C>T (p.Pro4Leu) 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: PM2_Supporting, BP4, BS3.
Met criteria codes
PM2_Supporting
absent from population databases
BS3
Functional (Kato, 94.3%% mean transactivation activity (>75%)) noDNE+noLOF (Giacomelli, p53WTNutlin3 Z-score -0.367(< 0.61) and Etoposide Z-score 0.356(> -0.21 ))
Functional (94.3%% mean transactivation activity (>75%)) PubMed:12826609
No dominant negative effect (p53WTNutlin3 Z-score -0.367(< 0.61)), and no loss of function (Etoposide Z-score 0.356(> -0.21 )). PubMed:30224644
BP4
Align-GVGD is C0 and BayesDel is 0.0629
Not Met criteria codes
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Functional (Kato, 94.3%% mean transactivation activity (>75%)) noDNE+noLOF (Giacomelli, p53WTNutlin3 Z-score -0.367(< 0.61) and Etoposide Z-score 0.356(> -0.21 ))
PS1
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
PP3
Align-GVGD is C0 and BayesDel is 0.0629
PM1
Not met (Not selected codon (175, 248, 273, 248, 245, 282, 249) or seen in cancerhotspots.org)
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
Observed in 1 60+ year old cancer free female from internal laboratory data
BP7
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
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.