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 computed assertion could be determined for this classification!

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

CA000249

141566 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 39a0504e-27a8-472f-946e-2df10c631aeb
Approved on: 2025-03-04
Published on: 2025-06-23

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

Likely Benign

Met criteria codes 3
PP3 PM2_Supporting BS3
Not Met criteria codes 15
BP7 BP4 PS1 PS2 PS3 PS4 PP1 PP4 PVS1 PM1 PM5 BA1 BS2 BS1 BS4

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6:c.511G>A variant in TP53 is a missense variant predicted to cause substitution of glutamic acid by lysine at amino acid 171 (p.Glu171Lys). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function (BS3; PMIDs: 12826609, 29979965, 30224644). Computational predictor scores (BayesDel = 0.3088; Align GVGD = Class C55) are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of > 15), evidence that correlates with impact to TP53 via protein change (PP3). In summary, this variant meets the criteria to be classified as Likely Benign for Li Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: PM2_Supporting, BS3, PP3. (Bayesian Points: -2; VCEP specifications version 2.3)
Met criteria codes
PP3
Computational predictor scores (BayesDel = 0.3088; Align GVGD = Class C55) are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of > 15), evidence that correlates with impact to TP53 via protein change (PP3).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
BS3
In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function (BS3; PMIDs: 12826609, 29979965, 30224644).
TA (RGC) supertrans PubMed:11313981
Not Met criteria codes
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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 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 0.5 points across 1 proband (PS4 not met; Internal lab contributors).
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
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
PM1
This variant does not reside within a region of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1 not met).
PM5
2 different missense variants (c.513G>T, p.Glu171Asp; c.512A>G, p.Glu171Gly) in the same codon have been reported (ClinVar Variation IDs: 2446885, 1745525). However, these variants do not meet criteria for PM5 code application (PM5 not met).
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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