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.329G>A (p.Arg110His)

CA000123

127808 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 00b45dfa-19f3-45de-975a-7b43bbc2be44
Approved on: 2020-08-11
Published on: 2020-08-14

HGVS expressions

NM_000546.5:c.329G>A
NM_000546.5(TP53):c.329G>A (p.Arg110His)
NM_001126112.2:c.329G>A
NM_001126113.2:c.329G>A
NM_001126114.2:c.329G>A
NM_001126118.1:c.212G>A
NM_001276695.1:c.212G>A
NM_001276696.1:c.212G>A
NM_001276760.1:c.212G>A
NM_001276761.1:c.212G>A
NM_001276695.2:c.212G>A
NM_001276696.2:c.212G>A
NM_001276760.2:c.212G>A
NM_001276761.2:c.212G>A
ENST00000269305.8:c.329G>A
ENST00000359597.8:n.329G>A
ENST00000413465.6:n.329G>A
ENST00000420246.6:c.329G>A
ENST00000445888.6:c.329G>A
ENST00000455263.6:c.329G>A
ENST00000503591.1:c.329G>A
ENST00000505014.5:n.585G>A
ENST00000508793.5:c.329G>A
ENST00000509690.5:c.-21-804G>A
ENST00000514944.5:c.96+342G>A
ENST00000604348.5:c.329G>A
ENST00000610292.4:c.212G>A
ENST00000610538.4:c.212G>A
ENST00000615910.4:n.329G>A
ENST00000617185.4:c.329G>A
ENST00000619485.4:c.212G>A
ENST00000620739.4:c.212G>A
ENST00000622645.4:c.212G>A
ENST00000635293.1:c.212G>A
NC_000017.11:g.7676040C>T
CM000679.2:g.7676040C>T
NC_000017.10:g.7579358C>T
CM000679.1:g.7579358C>T
NC_000017.9:g.7520083C>T
NG_017013.2:g.16511G>A
More

Likely Benign

Met criteria codes 3
BS2_Supporting BP4 BS3_Supporting
Not Met criteria codes 14
PP3 PP1 PP4 PM6 PM5 PM1 BA1 BS1 BS4 BP2 PS1 PS3 PS4 PS2

Evidence Links 4

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 (BP4). Transactivation assays show a partially functional variant 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_Supporting; PMID: 12826609, 30224644). This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; Internal laboratory contributor.) In summary, TP53 c.329G>A (p.Arg110His) 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, BS3_Supporting, BS2_Supporting.
Met criteria codes
BS2_Supporting
Not found in Flossies. Lab has 7 female cases that were cancer free at age 60 (SCV000184511.5).
PubMed:24728327
BP4
AGVGD C0 and BayeDel 0.072
BS3_Supporting
Partially functional variant + no_DNE + no_LOF
Not Met criteria codes
PP3
AGVGD C0 and BayeDel 0.072
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Do not use rule
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
Grantham score is 29. Three other variants found in codon have higher Grantham scores, 102, 103, and 108
PM1
Not in cancerhotpsots or designated hotspot
BA1
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
BP2
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
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
GeneDx has one case that meets Chompret (0.5 points) (SCV000149628.14). Identified in the literature in several women with breast cancer, one at age 32, two other reports with ages unconfirmed. (PMID: 23580068, 26976419, 2952266). Not enough points to meet.
PubMed:26976419
PubMed:29522266
PubMed:23580068
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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