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_001126112.2(TP53):c.250G>A (p.Ala84Thr)

CA000085

140833 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 37964f4e-7d50-4830-ba30-a640ab3afdb2
Approved on: 2020-08-11
Published on: 2020-08-14

HGVS expressions

NM_001126112.2:c.250G>A
NM_001126112.2(TP53):c.250G>A (p.Ala84Thr)
NC_000017.11:g.7676119C>T
CM000679.2:g.7676119C>T
NC_000017.10:g.7579437C>T
CM000679.1:g.7579437C>T
NC_000017.9:g.7520162C>T
NG_017013.2:g.16432G>A
NM_000546.5:c.250G>A
NM_001126113.2:c.250G>A
NM_001126114.2:c.250G>A
NM_001126118.1:c.133G>A
NM_001276695.1:c.133G>A
NM_001276696.1:c.133G>A
NM_001276760.1:c.133G>A
NM_001276761.1:c.133G>A
NM_001276695.2:c.133G>A
NM_001276696.2:c.133G>A
NM_001276760.2:c.133G>A
NM_001276761.2:c.133G>A
ENST00000269305.8:c.250G>A
ENST00000359597.8:n.250G>A
ENST00000413465.6:n.250G>A
ENST00000420246.6:c.250G>A
ENST00000445888.6:c.250G>A
ENST00000455263.6:c.250G>A
ENST00000503591.1:c.250G>A
ENST00000505014.5:n.506G>A
ENST00000508793.5:c.250G>A
ENST00000509690.5:c.-21-883G>A
ENST00000514944.5:c.96+263G>A
ENST00000604348.5:c.250G>A
ENST00000610292.4:c.133G>A
ENST00000610538.4:c.133G>A
ENST00000615910.4:n.250G>A
ENST00000617185.4:c.250G>A
ENST00000619485.4:c.133G>A
ENST00000620739.4:c.133G>A
ENST00000622645.4:c.133G>A
ENST00000635293.1:c.133G>A

Likely Benign

Met criteria codes 2
BS3 BP4
Not Met criteria codes 13
BS1 BS4 BS2 BP2 PS1 PS3 PS4 PS2 BA1 PP1 PM6 PM5 PM1

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 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, TP53 c.250G>A (p.Ala84Thr) meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the TP53 Expert Panel: BP4 and BS3.
Met criteria codes
BS3
present in KATO / noDNE+noLOF: p53WTNutlin3 Z-score < 0.61 and Etoposide Z-score > -0.21
BP4
AlignGVGD=C0; REVEL = 0,404; BayesDel = -0,0501613
Not Met criteria codes
BS1
3 alleles in gnomAD
BS4
Not in literature; no sufficient internal lab info
BS2
Not in literature; no sufficient internal lab info
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No other variants in ClinVar at this codon
PS3
present in KATO / noDNE+noLOF: p53WTNutlin3 Z-score < 0.61 and Etoposide Z-score > -0.21
PS4
Not in literature; no sufficient internal lab info
PS2
No de novo cases reported
BA1
3 alleles in gnomAD
PP1
Not in literature; no sufficient internal lab info
PM6
No de novo cases reported
PM5
No other variants in ClinVar at this codon
PM1
Not a hotspot. Not in cancerhotspots.org
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