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.572C>G (p.Pro191Arg)

CA000272

127816 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: dd649552-60d0-4411-92ac-361dc7acac10
Approved on: 2025-01-16
Published on: 2025-01-16

HGVS expressions

NM_000546.5:c.572C>G
NM_000546.5(TP53):c.572C>G (p.Pro191Arg)
NC_000017.11:g.7674959G>C
CM000679.2:g.7674959G>C
NC_000017.10:g.7578277G>C
CM000679.1:g.7578277G>C
NC_000017.9:g.7519002G>C
NG_017013.2:g.17592C>G
ENST00000503591.2:c.572C>G
ENST00000508793.6:c.572C>G
ENST00000509690.6:c.176C>G
ENST00000514944.6:c.293C>G
ENST00000604348.6:c.551C>G
ENST00000269305.9:c.572C>G
ENST00000269305.8:c.572C>G
ENST00000359597.8:c.572C>G
ENST00000413465.6:c.572C>G
ENST00000420246.6:c.572C>G
ENST00000445888.6:c.572C>G
ENST00000455263.6:c.572C>G
ENST00000504290.5:c.176C>G
ENST00000504937.5:c.176C>G
ENST00000505014.5:n.828C>G
ENST00000509690.5:c.176C>G
ENST00000510385.5:c.176C>G
ENST00000514944.5:c.293C>G
ENST00000574684.1:n.67+94C>G
ENST00000610292.4:c.455C>G
ENST00000610538.4:c.455C>G
ENST00000610623.4:c.95C>G
ENST00000615910.4:c.539C>G
ENST00000617185.4:c.572C>G
ENST00000618944.4:c.95C>G
ENST00000619186.4:c.95C>G
ENST00000619485.4:c.455C>G
ENST00000620739.4:c.455C>G
ENST00000622645.4:c.455C>G
ENST00000635293.1:c.455C>G
NM_001126112.2:c.572C>G
NM_001126113.2:c.572C>G
NM_001126114.2:c.572C>G
NM_001126115.1:c.176C>G
NM_001126116.1:c.176C>G
NM_001126117.1:c.176C>G
NM_001126118.1:c.455C>G
NM_001276695.1:c.455C>G
NM_001276696.1:c.455C>G
NM_001276697.1:c.95C>G
NM_001276698.1:c.95C>G
NM_001276699.1:c.95C>G
NM_001276760.1:c.455C>G
NM_001276761.1:c.455C>G
NM_001276695.2:c.455C>G
NM_001276696.2:c.455C>G
NM_001276697.2:c.95C>G
NM_001276698.2:c.95C>G
NM_001276699.2:c.95C>G
NM_001276760.2:c.455C>G
NM_001276761.2:c.455C>G
NM_000546.6:c.572C>G
NM_001126112.3:c.572C>G
NM_001126113.3:c.572C>G
NM_001126114.3:c.572C>G
NM_001126115.2:c.176C>G
NM_001126116.2:c.176C>G
NM_001126117.2:c.176C>G
NM_001126118.2:c.455C>G
NM_001276695.3:c.455C>G
NM_001276696.3:c.455C>G
NM_001276697.3:c.95C>G
NM_001276698.3:c.95C>G
NM_001276699.3:c.95C>G
NM_001276760.3:c.455C>G
NM_001276761.3:c.455C>G
More

Likely Benign

Met criteria codes 2
BS3 BP4
Not Met criteria codes 16
PS1 PS2 PS4 PS3 PP3 PP4 PP1 PM5 PM1 PM2 PVS1 BA1 BS2 BS4 BS1 BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6: c.572C>G variant in TP53 is a missense variant predicted to cause substitution of proline by arginine at amino acid 191 (p.Pro191Arg). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00005 (3/59996 alleles) in the Admixed American population (PM2, BS1, and BA1 are not met). 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 = 0.0942; Align GVGD Class 35) are below the recommended thresholds (BayesDel < 0.16 and > -0.008 and an Align GVGD Class ≤ 55), evidence that does not predict a damaging effect on TP53 via protein change. SpliceAI predicts that the variant has no impact on splicing (BP4). In summary, this variant meets the criteria to be classified as Likely Benign for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BS3, BP4. (Bayesian Points: -5; VCEP specifications version 2.2; 1/16/2025)
Met criteria codes
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).
BP4
Computational predictor scores (BayesDel = 0.0942; Align GVGD Class 35) are below the recommended thresholds (BayesDel < 0.16 and > -0.008 and an Align GVGD Class ≤ 55), evidence that does not predict a damaging effect on TP53 via protein change. SpliceAI predicts that the variant has no impact on splicing (BP4).
Not Met criteria codes
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
PS4
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
PP3
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
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Three different missense variants (c.572C>T (p.Pro191Leu), c.572C>A (p.Pro191His), c.571C>T (p.Pro191Ser)) in the same codon have been reported (ClinVar Variation IDs: 2703874, 853530, 1024017). However, the variants have not yet been curated to determine if they would be classified as pathogenic or likely pathogenic by the ClinGen TP53 VCEP’s specifications (PM5 not evaluated). Grantham: P>R: 103 P>L: 98 P>H: 77 P>S: 74
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).
PM2
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00005 (3/59996 alleles) in the Admixed American population (PM2, BS1, and BA1 are not met).
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00005 (3/59996 alleles) in the Admixed American population (PM2, BS1, and BA1 are not met).
BS2
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
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00005 (3/59996 alleles) in the Admixed American population (PM2, BS1, and BA1 are not met).
BP7
predicted possible new donor site by Human Splicing finder
Curation History
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