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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001126112.2(TP53):c.370T>A (p.Cys124Ser)

CA000138

182926 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 889f1ca0-a6ae-47bf-870f-3acbecfef5b7
Approved on: 2025-02-06
Published on: 2025-02-07

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
ENST00000503591.2:c.370T>A
ENST00000508793.6:c.370T>A
ENST00000509690.6:c.-21-763T>A
ENST00000514944.6:c.96+383T>A
ENST00000604348.6:c.370T>A
ENST00000269305.9:c.370T>A
ENST00000269305.8:c.370T>A
ENST00000359597.8:c.370T>A
ENST00000413465.6:c.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:c.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
More

Likely Benign

Met criteria codes 2
PP3_Moderate BS3
Not Met criteria codes 12
BP2 BP4 PS4 PS3 PP1 PM2 PM1 PM5 BA1 BS2 BS4 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.2.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6: c.370T>A variant in TP53 is a missense variant predicted to cause substitution of Cysteine by Serine at amino acid 124 (p.Cys124Ser). This variant received a total of 0.5 points across 1 proband. (PS4 not met; Internal lab contributors). In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function (BS3; PMIDs: 12826609, 29979965, 30224644). Computational predictor scores (BayesDel = 0.258 ; Align GVGD = Class C65 are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of 65), evidence that correlates with impact to TP53 via protein change (PP3_Moderate). In summary, this variant meets the criteria to be classified as Likely Benign based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BS3, PP3_Moderate (Bayesian Points: -2; VCEP specifications version 2.2; 2/6/2025).
Met criteria codes
PP3_Moderate
Computational predictor scores (BayesDel = 0.258 ; Align GVGD = Class C65 are above recommended thresholds (BayesDel > 0.16 and an Align GVGD Class of 65), evidence that correlates with impact to TP53 via protein change (PP3_Moderate).
BS3
In vitro assays performed in yeast and/or human cell lines showed functional transactivation and retained growth suppression activity indicating that this variant does not impact protein function(BS3; PMIDs: 12826609, 29979965, 30224644).
Not Met criteria codes
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
This variant received a total of 0.5 points across 1 proband. (PS4 not met; Internal lab contributors).
PS3
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
PM2
The highest population minor allele frequency in gnomAD v4.1.0 is 0.00004007 (3/74876 alleles) in the African/African American population (PM2, BS1, and BA1 are not met).
PM1
This variant does not reside within a region of TP53 that is defined as a mutational hotspot by the ClinGen TP53 VCEP (PM1 not met).
PM5
Two different missense variants (c.371G>C, p.Cys124Ser and c.370T>G, p.Cys124Gly) in the same codon have been reported (ClinVar Variation ID 1021578, 230661). However, the variants have not yet been curated to determine if they would be classified as pathogenic or likely pathogenic by the ClinGen TP53 VCEP’s specifications (PM5 not evaluated).
BA1
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
Curation History
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