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.322G>A (p.Gly108Ser)

CA000114

142431 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: d400b1c5-5b0e-4db7-af65-5d8c17b4a26b
Approved on: 2020-09-01
Published on: 2021-06-16

HGVS expressions

NM_000546.5:c.322G>A
NM_000546.5(TP53):c.322G>A (p.Gly108Ser)
NC_000017.11:g.7676047C>T
CM000679.2:g.7676047C>T
NC_000017.10:g.7579365C>T
CM000679.1:g.7579365C>T
NC_000017.9:g.7520090C>T
NG_017013.2:g.16504G>A
ENST00000269305.9:c.322G>A
ENST00000269305.8:c.322G>A
ENST00000359597.8:n.322G>A
ENST00000413465.6:n.322G>A
ENST00000420246.6:c.322G>A
ENST00000445888.6:c.322G>A
ENST00000455263.6:c.322G>A
ENST00000503591.1:c.322G>A
ENST00000505014.5:n.578G>A
ENST00000508793.5:c.322G>A
ENST00000509690.5:c.-21-811G>A
ENST00000514944.5:c.96+335G>A
ENST00000604348.5:c.322G>A
ENST00000610292.4:c.205G>A
ENST00000610538.4:c.205G>A
ENST00000615910.4:n.322G>A
ENST00000617185.4:c.322G>A
ENST00000619485.4:c.205G>A
ENST00000620739.4:c.205G>A
ENST00000622645.4:c.205G>A
ENST00000635293.1:c.205G>A
NM_001126112.2:c.322G>A
NM_001126113.2:c.322G>A
NM_001126114.2:c.322G>A
NM_001126118.1:c.205G>A
NM_001276695.1:c.205G>A
NM_001276696.1:c.205G>A
NM_001276760.1:c.205G>A
NM_001276761.1:c.205G>A
NM_001276695.2:c.205G>A
NM_001276696.2:c.205G>A
NM_001276760.2:c.205G>A
NM_001276761.2:c.205G>A
NM_000546.6:c.322G>A
NM_001126112.3:c.322G>A
NM_001126113.3:c.322G>A
NM_001126114.3:c.322G>A
NM_001126118.2:c.205G>A
NM_001276695.3:c.205G>A
NM_001276696.3:c.205G>A
NM_001276760.3:c.205G>A
NM_001276761.3:c.205G>A
More

Likely Benign

Met criteria codes 3
BS3_Supporting BS2_Supporting BP4
Not Met criteria codes 19
BS4 BS1 BP5 BP2 BP1 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM3 PM1 PM5 PM6 PM2

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). 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 contributors). In summary, TP53 c.322G>A (p.Gly108Ser) 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
BS3_Supporting
Partially functional (Kato) , noDNE & noLOF (Giacomelli), no LOF (Kotler)
BS2_Supporting
3 cases cancer free females at age 60+ years from Ambry internal data, 1 case from Color internal data, 6 cases from Invitae
BP4
Align GVGD Class C0, BayesDel 0.0347452, no predicted splicing effect (varseak, spliceAI)
Not Met criteria codes
BS4
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
BP5
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
BP1
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
Seen in 1/765 osteosarcoma patients unselected for FHx (no details about FHx or age of dx available) PMID: 25896519 1 case meeting Chompret criteria from Ambry internal data (PHx BC <31yo & FHx BC)
PS3
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
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
PP4
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
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not in a hotspot codon, not in cancerhotspots.org
PM5
One VUS at same codon in ClinVar
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
Present in 3 alleles in gnomAD v2.1.1
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.