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]
x This classification has been retracted/unpublished!
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.511G>A (p.Glu171Lys)

CA000249

141566 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 39a0504e-27a8-472f-946e-2df10c631aeb
Approved on: 2021-02-22
Published on: 2021-10-11

HGVS expressions

NM_000546.5:c.511G>A
NM_000546.5(TP53):c.511G>A (p.Glu171Lys)
NC_000017.11:g.7675101C>T
CM000679.2:g.7675101C>T
NC_000017.10:g.7578419C>T
CM000679.1:g.7578419C>T
NC_000017.9:g.7519144C>T
NG_017013.2:g.17450G>A
ENST00000503591.2:c.511G>A
ENST00000508793.6:c.511G>A
ENST00000509690.6:c.115G>A
ENST00000514944.6:c.232G>A
ENST00000604348.6:c.490G>A
ENST00000269305.9:c.511G>A
ENST00000269305.8:c.511G>A
ENST00000359597.8:c.511G>A
ENST00000413465.6:c.511G>A
ENST00000420246.6:c.511G>A
ENST00000445888.6:c.511G>A
ENST00000455263.6:c.511G>A
ENST00000504290.5:c.115G>A
ENST00000504937.5:c.115G>A
ENST00000505014.5:n.767G>A
ENST00000509690.5:c.115G>A
ENST00000510385.5:c.115G>A
ENST00000514944.5:c.232G>A
ENST00000574684.1:n.19G>A
ENST00000610292.4:c.394G>A
ENST00000610538.4:c.394G>A
ENST00000610623.4:c.34G>A
ENST00000615910.4:c.478G>A
ENST00000617185.4:c.511G>A
ENST00000618944.4:c.34G>A
ENST00000619186.4:c.34G>A
ENST00000619485.4:c.394G>A
ENST00000620739.4:c.394G>A
ENST00000622645.4:c.394G>A
ENST00000635293.1:c.394G>A
NM_001126112.2:c.511G>A
NM_001126113.2:c.511G>A
NM_001126114.2:c.511G>A
NM_001126115.1:c.115G>A
NM_001126116.1:c.115G>A
NM_001126117.1:c.115G>A
NM_001126118.1:c.394G>A
NM_001276695.1:c.394G>A
NM_001276696.1:c.394G>A
NM_001276697.1:c.34G>A
NM_001276698.1:c.34G>A
NM_001276699.1:c.34G>A
NM_001276760.1:c.394G>A
NM_001276761.1:c.394G>A
NM_001276695.2:c.394G>A
NM_001276696.2:c.394G>A
NM_001276697.2:c.34G>A
NM_001276698.2:c.34G>A
NM_001276699.2:c.34G>A
NM_001276760.2:c.394G>A
NM_001276761.2:c.394G>A
NM_000546.6:c.511G>A
NM_001126112.3:c.511G>A
NM_001126113.3:c.511G>A
NM_001126114.3:c.511G>A
NM_001126115.2:c.115G>A
NM_001126116.2:c.115G>A
NM_001126117.2:c.115G>A
NM_001126118.2:c.394G>A
NM_001276695.3:c.394G>A
NM_001276696.3:c.394G>A
NM_001276697.3:c.34G>A
NM_001276698.3:c.34G>A
NM_001276699.3:c.34G>A
NM_001276760.3:c.394G>A
NM_001276761.3:c.394G>A
More

Uncertain Significance

Met criteria codes 3
PP3 PM2_Supporting BS3
Not Met criteria codes 9
BP4 PS1 PS2 PS3 PS4 PM6 PM1 PM5 BS2

Evidence Links 0

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 65 (PP3_Moderate). 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, the clinical significance of TP53 c.511G>A (p.Glu171Lys) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, PP3, BS3.
Met criteria codes
PP3
AGVD is C55 and BayesDel is 0.308813 (> 0.16)
PM2_Supporting
Absent in gnomAD
BS3
Retained function by Kato (80.35%) and Giacomelli (p53WT_Nutlin-3_Z-score: 0.0976) and p53NULL_Etoposide_Z-score: 0.695) notDNE_notLOF, functional
Not Met criteria codes
BP4
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
PS2
No literature or internal data to support
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
One case meeting Chompret - not enough to apply this code.
PM6
No literature or internal data to support
PM1
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
BS2
Not found in FLOSSIES
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.