Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000546.5(TP53):c.28G>C (p.Val10Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10580966

231387 (ClinVar)

Gene: TP53

Condition: Li-Fraumeni syndrome 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d2f975d0-90d3-4610-83fe-fbdec78fa50d

Approved on: 2021-08-02

Published on: 2021-09-24

HGVS expressions

NM_000546.5:c.28G>C

NM_000546.5(TP53):c.28G>C (p.Val10Leu)

NC_000017.11:g.7676567C>G

CM000679.2:g.7676567C>G

NC_000017.10:g.7579885C>G

CM000679.1:g.7579885C>G

NC_000017.9:g.7520610C>G

NG_017013.2:g.15984G>C

ENST00000269305.9:c.28G>C

ENST00000269305.8:c.28G>C

ENST00000359597.8:n.28G>C

ENST00000413465.6:n.28G>C

ENST00000420246.6:c.28G>C

ENST00000445888.6:c.28G>C

ENST00000455263.6:c.28G>C

ENST00000503591.1:c.28G>C

ENST00000505014.5:n.167G>C

ENST00000508793.5:c.28G>C

ENST00000509690.5:c.-21-1331G>C

ENST00000514944.5:c.28G>C

ENST00000604348.5:c.28G>C

ENST00000610292.4:c.-207G>C

ENST00000610538.4:c.-90G>C

ENST00000615910.4:n.28G>C

ENST00000617185.4:c.28G>C

ENST00000619485.4:c.-90G>C

ENST00000620739.4:c.-90G>C

ENST00000622645.4:c.-90G>C

ENST00000635293.1:c.-90G>C

NM_001126112.2:c.28G>C

NM_001126113.2:c.28G>C

NM_001126114.2:c.28G>C

NM_001126118.1:c.-207G>C

NM_001276695.1:c.-90G>C

NM_001276696.1:c.-90G>C

NM_001276760.1:c.-90G>C

NM_001276761.1:c.-90G>C

NM_001276695.2:c.-90G>C

NM_001276696.2:c.-90G>C

NM_001276760.2:c.-90G>C

NM_001276761.2:c.-90G>C

NM_000546.6:c.28G>C

NM_001126112.3:c.28G>C

NM_001126113.3:c.28G>C

NM_001126114.3:c.28G>C

NM_001126118.2:c.-207G>C

NM_001276695.3:c.-90G>C

NM_001276696.3:c.-90G>C

NM_001276760.3:c.-90G>C

NM_001276761.3:c.-90G>C

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS3 BP4 BS2_Supporting PM2_Supporting

BS4 BS1 BP5 BP2 PS2 PS4 PS1 PS3 PP1 PP3 PM6 PM1 PM5 BA1

Evidence Links 0

Expert Panel

TP53 VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

TP53 VCEP

Transactivation assays show 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 or Class C15 (BP4). This variant has been observed in 4 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org) In summary, NM_000546.5(TP53):c.28G>C (p.Val10Leu) 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: BS3, PM2_Supporting, BP4, BS2_Supporting.

BS3

BS3: Transactivation assays show 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) [Giacomelli Nutlin = -0.687144839; Giacomelli Toposide = .158722141; Kato Transactivation assay = 120.7]

BP4

BP4: This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). [A-GVGD = C0; BayesDel = -0.0594. ]

BS2_Supporting

This variant has been observed in 2-7 60+ year old females without a cancer diagnosis (BS2_Supporting; internal laboratory contributors). Not present in FLOSSIES.

PM2_Supporting

This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org).

BS4