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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000546.5(TP53):c.436T>G (p.Trp146Gly)

CA000190

186587 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4e4e51a2-bf4a-44a4-9fb7-5d5816cdfb92
Approved on: 2020-09-04
Published on: 2021-06-16

HGVS expressions

NM_000546.5:c.436T>G
NM_000546.5(TP53):c.436T>G (p.Trp146Gly)
NC_000017.11:g.7675176A>C
CM000679.2:g.7675176A>C
NC_000017.10:g.7578494A>C
CM000679.1:g.7578494A>C
NC_000017.9:g.7519219A>C
NG_017013.2:g.17375T>G
ENST00000269305.9:c.436T>G
ENST00000269305.8:c.436T>G
ENST00000359597.8:n.436T>G
ENST00000413465.6:n.436T>G
ENST00000420246.6:c.436T>G
ENST00000445888.6:c.436T>G
ENST00000455263.6:c.436T>G
ENST00000504290.5:c.40T>G
ENST00000504937.5:c.40T>G
ENST00000505014.5:n.692T>G
ENST00000508793.5:c.436T>G
ENST00000509690.5:c.40T>G
ENST00000510385.5:c.40T>G
ENST00000514944.5:c.157T>G
ENST00000604348.5:c.415T>G
ENST00000610292.4:c.319T>G
ENST00000610538.4:c.319T>G
ENST00000610623.4:c.-42T>G
ENST00000615910.4:n.403T>G
ENST00000617185.4:c.436T>G
ENST00000618944.4:c.-42T>G
ENST00000619186.4:c.-42T>G
ENST00000619485.4:c.319T>G
ENST00000620739.4:c.319T>G
ENST00000622645.4:c.319T>G
ENST00000635293.1:c.319T>G
NM_001126112.2:c.436T>G
NM_001126113.2:c.436T>G
NM_001126114.2:c.436T>G
NM_001126115.1:c.40T>G
NM_001126116.1:c.40T>G
NM_001126117.1:c.40T>G
NM_001126118.1:c.319T>G
NM_001276695.1:c.319T>G
NM_001276696.1:c.319T>G
NM_001276697.1:c.-42T>G
NM_001276698.1:c.-42T>G
NM_001276699.1:c.-42T>G
NM_001276760.1:c.319T>G
NM_001276761.1:c.319T>G
NM_001276695.2:c.319T>G
NM_001276696.2:c.319T>G
NM_001276697.2:c.-42T>G
NM_001276698.2:c.-42T>G
NM_001276699.2:c.-42T>G
NM_001276760.2:c.319T>G
NM_001276761.2:c.319T>G
NM_000546.6:c.436T>G
NM_001126112.3:c.436T>G
NM_001126113.3:c.436T>G
NM_001126114.3:c.436T>G
NM_001126115.2:c.40T>G
NM_001126116.2:c.40T>G
NM_001126117.2:c.40T>G
NM_001126118.2:c.319T>G
NM_001276695.3:c.319T>G
NM_001276696.3:c.319T>G
NM_001276697.3:c.-42T>G
NM_001276698.3:c.-42T>G
NM_001276699.3:c.-42T>G
NM_001276760.3:c.319T>G
NM_001276761.3:c.319T>G

Uncertain Significance

Met criteria codes 3
BP4 PS4_Supporting PM2_Supporting
Not Met criteria codes 11
BS2 BS4 BS3 BS1 PS2 PS3 PS1 BA1 PP3 PM6 PM5

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). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). This variant has been reported in 1 proband meeting Classic LFS criteria (PS4_Supporting; NIH). In summary, the clinical significance of TP53 c.436T>G (p.Trp146Gly) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: PM2_Supporting, PS4_Supporting, BP4.
Met criteria codes
BP4
BayesDel = 0.0351; aGVGD = C0
PS4_Supporting
1 proband meeting classical LFS in NIH cohort (sister also has CHEK2 1100delC variant, but VCEP agrees this should not preclude the family)
PM2_Supporting
Absent from gnomAD
Not Met criteria codes
BS2
Not seen in FLOSSIES. Internal lab data not reviewed
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Non-functional (Kato); LOF but not DNE (Giacomelli); not LOF (Kotler)
BS1
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
Non-functional (Kato); LOF but not DNE (Giacomelli); not LOF (Kotler)
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
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
PM5
No. Only other change reported is nonsense, Trp146Ter (ClinVar: 428890, P)
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