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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.107C>A (p.Pro36Gln)

CA000031

141597 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6b107a24-eff7-4b60-b98a-3d8682be8658

HGVS expressions

NM_000546.5:c.107C>A
NM_000546.5(TP53):c.107C>A (p.Pro36Gln)
NC_000017.11:g.7676262G>T
CM000679.2:g.7676262G>T
NC_000017.10:g.7579580G>T
CM000679.1:g.7579580G>T
NC_000017.9:g.7520305G>T
NG_017013.2:g.16289C>A
ENST00000269305.8:c.107C>A
ENST00000359597.8:n.107C>A
ENST00000413465.6:n.107C>A
ENST00000420246.6:c.107C>A
ENST00000445888.6:c.107C>A
ENST00000455263.6:c.107C>A
ENST00000503591.1:c.107C>A
ENST00000508793.5:c.107C>A
ENST00000509690.5:c.-21-1026C>A
ENST00000514944.5:c.96+120C>A
ENST00000604348.5:c.107C>A
ENST00000610292.4:c.-11C>A
ENST00000610538.4:c.-11C>A
ENST00000615910.4:n.107C>A
ENST00000617185.4:c.107C>A
ENST00000619485.4:c.-11C>A
ENST00000620739.4:c.-11C>A
ENST00000622645.4:c.-11C>A
ENST00000635293.1:c.-11C>A
NM_001126112.2:c.107C>A
NM_001126113.2:c.107C>A
NM_001126114.2:c.107C>A
NM_001126118.1:c.-11C>A
NM_001276695.1:c.-11C>A
NM_001276696.1:c.-11C>A
NM_001276760.1:c.-11C>A
NM_001276761.1:c.-11C>A
NM_001276695.2:c.-11C>A
NM_001276696.2:c.-11C>A
NM_001276760.2:c.-11C>A
NM_001276761.2:c.-11C>A
NM_000546.6:c.107C>A
NM_001126112.3:c.107C>A
NM_001126113.3:c.107C>A
NM_001126114.3:c.107C>A
NM_001126118.2:c.-11C>A
NM_001276695.3:c.-11C>A
NM_001276696.3:c.-11C>A
NM_001276760.3:c.-11C>A
NM_001276761.3:c.-11C>A

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"
Met criteria codes 3
PM2_Supporting BS3 BP4
Not Met criteria codes 14
PS1 PS4 PS2 PS3 PP1 PP3 PM6 PM1 PM5 BA1 BS2 BS4 BS1 BP2

Evidence Links 0

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). Transactivation assays show [retained/supertransactivation] 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). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, the clinical significance of TP53 c.107C>A (p.Pro36Gln) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, BS3, BP4.
Met criteria codes
PM2_Supporting
Absent from Exac, gnomAD, 1000G where the region of the variant was covered
BS3
Functional (Kato, 79.35% mean transactivation activity (>75%)) noDNE+noLOF (Giacomelli, p53WTNutlin3 Z-score -0.188 (< 0.61) and Etoposide Z-score 0.651 (> -0.21 ))
BP4
Bayesdel is -0.07 and AGVGD is C0
Not Met criteria codes
PS1
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Functional (Kato, 79.35% mean transactivation activity (>75%)) noDNE+noLOF (Giacomelli, p53WTNutlin3 Z-score -0.188 (< 0.61) and Etoposide Z-score 0.651 (> -0.21 ))
PP1
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
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
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
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
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
Approved on: 2021-02-22
Published on: 2021-02-22
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