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.886C>T (p.His296Tyr)

CA000474

132973 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: fd1fd761-b5ce-4519-9c0a-a4688f12b30b
Approved on: 2020-08-11
Published on: 2020-08-14

HGVS expressions

NM_000546.5:c.886C>T
NM_000546.5(TP53):c.886C>T (p.His296Tyr)
NM_001126112.2:c.886C>T
NM_001126113.2:c.886C>T
NM_001126114.2:c.886C>T
NM_001126115.1:c.490C>T
NM_001126116.1:c.490C>T
NM_001126117.1:c.490C>T
NM_001126118.1:c.769C>T
NM_001276695.1:c.769C>T
NM_001276696.1:c.769C>T
NM_001276697.1:c.409C>T
NM_001276698.1:c.409C>T
NM_001276699.1:c.409C>T
NM_001276760.1:c.769C>T
NM_001276761.1:c.769C>T
NM_001276695.2:c.769C>T
NM_001276696.2:c.769C>T
NM_001276697.2:c.409C>T
NM_001276698.2:c.409C>T
NM_001276699.2:c.409C>T
NM_001276760.2:c.769C>T
NM_001276761.2:c.769C>T
ENST00000269305.8:c.886C>T
ENST00000359597.8:n.886C>T
ENST00000413465.6:n.782+447C>T
ENST00000420246.6:c.886C>T
ENST00000445888.6:c.886C>T
ENST00000455263.6:c.886C>T
ENST00000504290.5:c.490C>T
ENST00000504937.5:c.490C>T
ENST00000509690.5:c.490C>T
ENST00000510385.5:c.490C>T
ENST00000610292.4:c.769C>T
ENST00000610538.4:c.769C>T
ENST00000610623.4:c.409C>T
ENST00000615910.4:n.853C>T
ENST00000617185.4:c.886C>T
ENST00000618944.4:c.409C>T
ENST00000619186.4:c.409C>T
ENST00000619485.4:c.769C>T
ENST00000620739.4:c.769C>T
ENST00000622645.4:c.769C>T
ENST00000635293.1:c.769C>T
NC_000017.11:g.7673734G>A
CM000679.2:g.7673734G>A
NC_000017.10:g.7577052G>A
CM000679.1:g.7577052G>A
NC_000017.9:g.7517777G>A
NG_017013.2:g.18817C>T
More

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 12
PS3 PS4 PS1 BA1 PM1 PM5 PP1 PP3 BS1 BS4 BS2 BP2

Evidence Links 0

Expert Panel

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). Additionally, this variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 or Class C15 (BP4). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). In summary, the clinical significance of TP53 c.886C>T (p.His296Tyr) is likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, PM2_Supporting.
Met criteria codes
PM2_Supporting
absent from gnomAD (v2.1.1 and v3)
BS3
Transactivation assays show super transactivation 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.
BP4
BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0
Not Met criteria codes
PS3
see BP3
PS4
Absent from cases and controls in literature and databases.
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
PM1
Not in hot spot codons per VCEP rules. Not present in cancerhotspots database.
PM5
There is a variant in the same codon in ClinVar, c.887A>G (p.His296Arg), but the submission has zero stars and based on the provided information does not meet criteria for pathogenicity (one submitter, no details provided, allelic origin = somatic)
PP1
No segregation data available.
PP3
see BP4
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No segregation data available.
BS2
Absent from gnomAD, FLOSSIES and no cases in the literature.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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