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.97-3C>T

CA000514

187457 (ClinVar)

Gene: TP53
Condition: Li-Fraumeni syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 5281b614-fb59-400c-b34d-b56faa078da3
Approved on: 2025-04-11
Published on: 2025-06-23

HGVS expressions

NM_001126112.2:c.97-3C>T
NM_001126112.2(TP53):c.97-3C>T
NC_000017.11:g.7676275G>A
CM000679.2:g.7676275G>A
NC_000017.10:g.7579593G>A
CM000679.1:g.7579593G>A
NC_000017.9:g.7520318G>A
NG_017013.2:g.16276C>T
ENST00000503591.2:c.97-3C>T
ENST00000508793.6:c.97-3C>T
ENST00000509690.6:c.-21-1039C>T
ENST00000514944.6:c.96+107C>T
ENST00000604348.6:c.97-3C>T
ENST00000269305.9:c.97-3C>T
ENST00000269305.8:c.97-3C>T
ENST00000359597.8:c.97-3C>T
ENST00000413465.6:c.97-3C>T
ENST00000420246.6:c.97-3C>T
ENST00000445888.6:c.97-3C>T
ENST00000455263.6:c.97-3C>T
ENST00000503591.1:c.97-3C>T
ENST00000505014.5:n.353-3C>T
ENST00000508793.5:c.97-3C>T
ENST00000509690.5:c.-21-1039C>T
ENST00000514944.5:c.96+107C>T
ENST00000604348.5:c.97-3C>T
ENST00000610292.4:c.-21-3C>T
ENST00000610538.4:c.-21-3C>T
ENST00000615910.4:c.97-3C>T
ENST00000617185.4:c.97-3C>T
ENST00000619485.4:c.-21-3C>T
ENST00000620739.4:c.-21-3C>T
ENST00000622645.4:c.-21-3C>T
ENST00000635293.1:c.-21-3C>T
NM_000546.5:c.97-3C>T
NM_001126113.2:c.97-3C>T
NM_001126114.2:c.97-3C>T
NM_001126118.1:c.-21-3C>T
NM_001276695.1:c.-21-3C>T
NM_001276696.1:c.-21-3C>T
NM_001276760.1:c.-21-3C>T
NM_001276761.1:c.-21-3C>T
NM_001276695.2:c.-21-3C>T
NM_001276696.2:c.-21-3C>T
NM_001276760.2:c.-21-3C>T
NM_001276761.2:c.-21-3C>T
NM_000546.6:c.97-3C>T
NM_001126112.3:c.97-3C>T
NM_001126113.3:c.97-3C>T
NM_001126114.3:c.97-3C>T
NM_001126118.2:c.-21-3C>T
NM_001276695.3:c.-21-3C>T
NM_001276696.3:c.-21-3C>T
NM_001276760.3:c.-21-3C>T
NM_001276761.3:c.-21-3C>T
More

Benign

Met criteria codes 3
PM2_Supporting BS2 BP7_Strong
Not Met criteria codes 13
BA1 PM6 PM1 BS4 BS3 BS1 BP4 PS2 PS4 PS3 PP4 PP1 PP3

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 2.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
TP53 VCEP
The NM_000546.6:c.97-3C>T variant in TP53 is an intronic variant located in intron 3. This variant has been observed in at least 8 heterozygous unrelated females from the same data source with no personal history of cancer prior to age 60 years and no personal history of sarcoma at any age (BS2; Internal lab contributor). This variant has an allele frequency of 0.000004337 (7/1614174 alleles) across gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00003) for PM2_Supporting and has a subpopulation allele frequency of <0.00004 in all non-bottleneck populations with 2 or more alleles present (PM2_Supporting). The c.97-3C>T variant is an intronic variant for which RNA splicing assay data demonstrates no splicing aberration (Internal lab contributors). To our knowledge, functional assays have not been reported for this variant (PS3/BS3 not met). In summary, this variant meets the criteria to be classified as Benign for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BS2, PM2_Supporting, BP7_Strong (RNA). (Bayesian Points: -7; VCEP specifications version 2.3).
Met criteria codes
PM2_Supporting
This variant has an allele frequency of 0.000004337 (7/1614174 alleles) across gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00003) for PM2_Supporting and has a subpopulation allele frequency of <0.00004 in all non-bottleneck populations with 2 or more alleles present (PM2_Supporting).
BS2
This variant has been observed in at least 8 heterozygous unrelated females from the same data source with no personal history of cancer prior to age 60 years and no personal history of sarcoma at any age (BS2; Internal lab contributor).
BP7_Strong
The c.97-3C>T variant is an intronic variant for which RNA splicing assay data demonstrates no splicing aberration (Internal lab contributors).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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).
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
To our knowledge, functional assays have not been reported for this variant (PS3/BS3 not met).
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
Predicted impact on splicing based on the computational splicing predictor SpliceAI is unclear (score > 0.10 and <0.20) (PP3 and BP4 not met).
PS2
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
To our knowledge, functional assays have not been reported for this variant (PS3/BS3 not met).
PP4
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
PP3
Predicted impact on splicing based on the computational splicing predictor SpliceAI is unclear (score > 0.10 and <0.20) (PP3 and BP4 not met).
Curation History
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