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 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.1136G>A (p.Arg379His)

CA10584584

246221 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9bd50b93-5f12-44c4-81f6-e1a9ced34840
Approved on: 2021-08-12
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.1136G>A
NM_000546.5(TP53):c.1136G>A (p.Arg379His)
NC_000017.11:g.7669655C>T
CM000679.2:g.7669655C>T
NC_000017.10:g.7572973C>T
CM000679.1:g.7572973C>T
NC_000017.9:g.7513698C>T
NG_017013.2:g.22896G>A
ENST00000503591.2:c.1136G>A
ENST00000508793.6:c.1136G>A
ENST00000509690.6:c.740G>A
ENST00000514944.6:c.857G>A
ENST00000604348.6:c.1115G>A
ENST00000269305.9:c.1136G>A
ENST00000269305.8:c.1136G>A
ENST00000359597.8:c.994-3411G>A
ENST00000413465.6:c.782+4526G>A
ENST00000420246.6:c.*243G>A
ENST00000445888.6:c.1136G>A
ENST00000455263.6:c.*155G>A
ENST00000504290.5:c.*155G>A
ENST00000504937.5:c.740G>A
ENST00000510385.5:c.*243G>A
ENST00000576024.1:c.89G>A
ENST00000610292.4:c.1019G>A
ENST00000610538.4:c.*155G>A
ENST00000610623.4:c.*155G>A
ENST00000615910.4:c.1103G>A
ENST00000617185.4:c.*243G>A
ENST00000618944.4:c.*243G>A
ENST00000619186.4:c.659G>A
ENST00000619485.4:c.1019G>A
ENST00000620739.4:c.1019G>A
ENST00000622645.4:c.*243G>A
ENST00000635293.1:c.983+954G>A
NM_001126112.2:c.1136G>A
NM_001126113.2:c.*155G>A
NM_001126114.2:c.*243G>A
NM_001126115.1:c.740G>A
NM_001126116.1:c.*243G>A
NM_001126117.1:c.*155G>A
NM_001126118.1:c.1019G>A
NM_001276695.1:c.*155G>A
NM_001276696.1:c.*243G>A
NM_001276697.1:c.659G>A
NM_001276698.1:c.*243G>A
NM_001276699.1:c.*155G>A
NM_001276760.1:c.1019G>A
NM_001276761.1:c.1019G>A
NM_001276695.2:c.*155G>A
NM_001276696.2:c.*243G>A
NM_001276697.2:c.659G>A
NM_001276698.2:c.*243G>A
NM_001276699.2:c.*155G>A
NM_001276760.2:c.1019G>A
NM_001276761.2:c.1019G>A
NM_000546.6:c.1136G>A
NM_001126112.3:c.1136G>A
NM_001126113.3:c.*155G>A
NM_001126114.3:c.*243G>A
NM_001126115.2:c.740G>A
NM_001126116.2:c.*243G>A
NM_001126117.2:c.*155G>A
NM_001126118.2:c.1019G>A
NM_001276695.3:c.*155G>A
NM_001276696.3:c.*243G>A
NM_001276697.3:c.659G>A
NM_001276698.3:c.*243G>A
NM_001276699.3:c.*155G>A
NM_001276760.3:c.1019G>A
NM_001276761.3:c.1019G>A
More

Likely Benign

Met criteria codes 2
BS3 BP4
Not Met criteria codes 16
PS1 PS2 PS3 PS4 BA1 PP1 PP3 PM6 PM2 PM1 PM5 BS2 BS1 BS4 BP1 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). Additionally, 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). In summary, TP53 c.1136G>A; p.Arg379His 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: BP4 and BS3.
Met criteria codes
BS3
Retained function by Kato et al. and Giacomelli et al.
BP4
Align-GVGD (Class C0) and BayesDel (-0.0720)
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No reports of variant in provided internal data. Report in the literature (PMID: 26086041) does not meet Classical or Revised Chompret criteria.
BA1
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 (Class C0) and BayesDel (-0.0720), no predicted impact on splicing
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Total allele frequency in gnomAD 2/282792 (0.0007%)
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Only VUS/Likely Benign reported in Clinvar
BS2
Not identified in FLOSSIES, nor in 2 or more cancer free 60+ women from submitted internal lab data
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
BP1
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
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