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.353C>T (p.Thr118Ile)

CA16620635

419837 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: fc7cc0ba-f84e-46c8-acb3-ef170d24b394
Approved on: 2021-08-03
Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.353C>T
NM_000546.5(TP53):c.353C>T (p.Thr118Ile)
NC_000017.11:g.7676016G>A
CM000679.2:g.7676016G>A
NC_000017.10:g.7579334G>A
CM000679.1:g.7579334G>A
NC_000017.9:g.7520059G>A
NG_017013.2:g.16535C>T
ENST00000269305.9:c.353C>T
ENST00000269305.8:c.353C>T
ENST00000359597.8:n.353C>T
ENST00000413465.6:n.353C>T
ENST00000420246.6:c.353C>T
ENST00000445888.6:c.353C>T
ENST00000455263.6:c.353C>T
ENST00000503591.1:c.353C>T
ENST00000505014.5:n.609C>T
ENST00000508793.5:c.353C>T
ENST00000509690.5:c.-21-780C>T
ENST00000514944.5:c.96+366C>T
ENST00000604348.5:c.353C>T
ENST00000610292.4:c.236C>T
ENST00000610538.4:c.236C>T
ENST00000615910.4:n.340+9C>T
ENST00000617185.4:c.353C>T
ENST00000619485.4:c.236C>T
ENST00000620739.4:c.236C>T
ENST00000622645.4:c.236C>T
ENST00000635293.1:c.236C>T
NM_001126112.2:c.353C>T
NM_001126113.2:c.353C>T
NM_001126114.2:c.353C>T
NM_001126118.1:c.236C>T
NM_001276695.1:c.236C>T
NM_001276696.1:c.236C>T
NM_001276760.1:c.236C>T
NM_001276761.1:c.236C>T
NM_001276695.2:c.236C>T
NM_001276696.2:c.236C>T
NM_001276760.2:c.236C>T
NM_001276761.2:c.236C>T
NM_000546.6:c.353C>T
NM_001126112.3:c.353C>T
NM_001126113.3:c.353C>T
NM_001126114.3:c.353C>T
NM_001126118.2:c.236C>T
NM_001276695.3:c.236C>T
NM_001276696.3:c.236C>T
NM_001276760.3:c.236C>T
NM_001276761.3:c.236C>T
More

Uncertain Significance

Met criteria codes 4
PP3_Moderate BS2_Supporting BS3 PM2_Supporting
Not Met criteria codes 12
BA1 PS2 PS3 PS1 PP1 PM6 PM1 PM5 BS4 BS1 BP2 BP4

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has a BayesDel score > 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). This variant has been observed in 2 60+ year old females without a cancer diagnosis (BS2_Supporting; Ambry Genetics). 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, the clinical significance of TP53 c.353C>T (p.Thr118Ile) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, PP3_Moderate, BS2_Supporting, BS3
Met criteria codes
PP3_Moderate
AlignGVGD C65, BayesDel 0.34663
BS2_Supporting
2 females cancer free at age 60 in Ambry internal data
BS3
Kato functional, Giacomelli noLOF/noDNE, Kotler noLOF
Functional PubMed:12826609
noLOF/noDNE PubMed:30224644
noLOF PubMed:29979965
PM2_Supporting
Absent in gnomAD v2.1.1 (non-cancer)
Not Met criteria codes
BA1
Absent in gnomAD v2.1.1 (non-cancer)
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Kato functional, Giacomelli noLOF/noDNE, Kotler noLOF
PS1
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No hotspot, not in cancerhotspots.org
PM5
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
Absent in gnomAD v2.1.1 (non-cancer)
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
AlignGVGD C65, BayesDel 0.34663
Curation History
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