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_001126112.2(TP53):c.370T>A (p.Cys124Ser)

CA000138

182926 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 889f1ca0-a6ae-47bf-870f-3acbecfef5b7
Approved on: 2022-01-10
Published on: 2022-01-10

HGVS expressions

NM_001126112.2:c.370T>A
NM_001126112.2(TP53):c.370T>A (p.Cys124Ser)
NC_000017.11:g.7675999A>T
CM000679.2:g.7675999A>T
NC_000017.10:g.7579317A>T
CM000679.1:g.7579317A>T
NC_000017.9:g.7520042A>T
NG_017013.2:g.16552T>A
ENST00000269305.9:c.370T>A
ENST00000269305.8:c.370T>A
ENST00000359597.8:n.370T>A
ENST00000413465.6:n.370T>A
ENST00000420246.6:c.370T>A
ENST00000445888.6:c.370T>A
ENST00000455263.6:c.370T>A
ENST00000503591.1:c.370T>A
ENST00000505014.5:n.626T>A
ENST00000508793.5:c.370T>A
ENST00000509690.5:c.-21-763T>A
ENST00000514944.5:c.96+383T>A
ENST00000604348.5:c.370T>A
ENST00000610292.4:c.253T>A
ENST00000610538.4:c.253T>A
ENST00000615910.4:n.340+26T>A
ENST00000617185.4:c.370T>A
ENST00000619485.4:c.253T>A
ENST00000620739.4:c.253T>A
ENST00000622645.4:c.253T>A
ENST00000635293.1:c.253T>A
NM_000546.5:c.370T>A
NM_001126113.2:c.370T>A
NM_001126114.2:c.370T>A
NM_001126118.1:c.253T>A
NM_001276695.1:c.253T>A
NM_001276696.1:c.253T>A
NM_001276760.1:c.253T>A
NM_001276761.1:c.253T>A
NM_001276695.2:c.253T>A
NM_001276696.2:c.253T>A
NM_001276760.2:c.253T>A
NM_001276761.2:c.253T>A
NM_000546.6:c.370T>A
NM_001126112.3:c.370T>A
NM_001126113.3:c.370T>A
NM_001126114.3:c.370T>A
NM_001126118.2:c.253T>A
NM_001276695.3:c.253T>A
NM_001276696.3:c.253T>A
NM_001276760.3:c.253T>A
NM_001276761.3:c.253T>A
NM_000546.6(TP53):c.370T>A (p.Cys124Ser)
More

Uncertain Significance

Met criteria codes 2
PP3_Moderate BS3
Not Met criteria codes 12
PM2 PM1 PM5 BA1 BS4 BS1 BS2 BP2 PS4 PS3 PS1 PP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
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). This variant has a BayesDel score greater than or equal to 0.16 and Align GVGD (Zebrafish) is Class 65 (PP3_Moderate). In summary, the clinical significance of TP53 c.370T>A (p.Cys124Ser) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, PP3_Moderate.
Met criteria codes
PP3_Moderate
BayesDel score is 0.258 and aGVGD score is C65
BS3
Present in Kato (92,45 = Functional)/p53WTNutlin3 Z-score < 0.61 (0,30) and Etoposide Z-score > -0.21 (0,017)
Not Met criteria codes
PM2
Not met - Allele count =3; gnomAD = 0,001%
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
Not met - Allele count =3; gnomAD = 0,001%
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
BS2
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
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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