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_000546.6(TP53):c.414C>T (p.Ala138=)

CA497925710

482234 (ClinVar)

Gene: TP53 (HGNC:7157)
Condition: Li-Fraumeni syndrome (MONDO:0018875)
Inheritance Mode: Autosomal dominant inheritance
UUID: 0fbddfff-af44-44e7-8fc8-ba584e35fc96
Approved on: 2025-06-05
Published on: 2025-07-18

HGVS expressions

NM_000546.6:c.414C>T
NM_000546.6(TP53):c.414C>T (p.Ala138=)
NC_000017.11:g.7675198G>A
CM000679.2:g.7675198G>A
NC_000017.10:g.7578516G>A
CM000679.1:g.7578516G>A
NC_000017.9:g.7519241G>A
NG_017013.2:g.17353C>T
ENST00000503591.2:c.414C>T
ENST00000508793.6:c.414C>T
ENST00000509690.6:c.18C>T
ENST00000514944.6:c.135C>T
ENST00000604348.6:c.393C>T
ENST00000269305.9:c.414C>T
ENST00000269305.8:c.414C>T
ENST00000359597.8:c.414C>T
ENST00000413465.6:c.414C>T
ENST00000420246.6:c.414C>T
ENST00000445888.6:c.414C>T
ENST00000455263.6:c.414C>T
ENST00000504290.5:c.18C>T
ENST00000504937.5:c.18C>T
ENST00000505014.5:n.670C>T
ENST00000508793.5:c.414C>T
ENST00000509690.5:c.18C>T
ENST00000510385.5:c.18C>T
ENST00000514944.5:c.135C>T
ENST00000604348.5:c.393C>T
ENST00000610292.4:c.297C>T
ENST00000610538.4:c.297C>T
ENST00000610623.4:c.-64C>T
ENST00000615910.4:c.381C>T
ENST00000617185.4:c.414C>T
ENST00000618944.4:c.-64C>T
ENST00000619186.4:c.-64C>T
ENST00000619485.4:c.297C>T
ENST00000620739.4:c.297C>T
ENST00000622645.4:c.297C>T
ENST00000635293.1:c.297C>T
NM_000546.5:c.414C>T
NM_001126112.2:c.414C>T
NM_001126113.2:c.414C>T
NM_001126114.2:c.414C>T
NM_001126115.1:c.18C>T
NM_001126116.1:c.18C>T
NM_001126117.1:c.18C>T
NM_001126118.1:c.297C>T
NM_001276695.1:c.297C>T
NM_001276696.1:c.297C>T
NM_001276697.1:c.-64C>T
NM_001276698.1:c.-64C>T
NM_001276699.1:c.-64C>T
NM_001276760.1:c.297C>T
NM_001276761.1:c.297C>T
NM_001276695.2:c.297C>T
NM_001276696.2:c.297C>T
NM_001276697.2:c.-64C>T
NM_001276698.2:c.-64C>T
NM_001276699.2:c.-64C>T
NM_001276760.2:c.297C>T
NM_001276761.2:c.297C>T
NM_001126112.3:c.414C>T
NM_001126113.3:c.414C>T
NM_001126114.3:c.414C>T
NM_001126115.2:c.18C>T
NM_001126116.2:c.18C>T
NM_001126117.2:c.18C>T
NM_001126118.2:c.297C>T
NM_001276695.3:c.297C>T
NM_001276696.3:c.297C>T
NM_001276697.3:c.-64C>T
NM_001276698.3:c.-64C>T
NM_001276699.3:c.-64C>T
NM_001276760.3:c.297C>T
NM_001276761.3:c.297C>T
More

Likely Benign

Met criteria codes 3
BP7 BP4 PM2_Supporting
Not Met criteria codes 21
BA1 BP5 BP2 BP3 BP1 BS4 BS3 BS1 BS2 PP4 PP1 PP3 PP2 PM6 PS2 PS4 PS3 PM1 PM3 PM4 PVS1

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 c.414C>T (p.Ala138=) variant is a synonymous (silent) variant outside of the core splice motif, and BP4 code is met for splicing prediction (BP4, BP7). To our knowledge, this variant has not been reported in individuals meeting classical LFS or Chompret criteria (PS4 not met). This variant has an allele frequency of 6.195e-7 (1/1614158 alleles) across gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00003) for PM2_Supporting and has no more than one allele per non-bottleneck subpopulation (PM2_Supporting). To our knowledge, functional assays have not been reported for this variant (PS3/BS3 not met). The computational splicing predictor SpliceAI gives a score of [0.01], predicting that the variant has no impact on splicing (score threshold ≤ 0.10) (BP4). In summary, this variant meets the criteria to be classified as likely benign for Li Fraumeni syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen TP53 VCEP: BP4, BP7, PM2_Supporting. (Bayesian Points: -1; VCEP specifications version 2.3)
Met criteria codes
BP7
The c.414C>T (p.Ala138=) variant is a synonymous (silent) variant outside of the core splice motif, and BP4 code is met for splicing prediction (BP4, BP7).
BP4
The computational splicing predictor SpliceAI gives a score of [0.01], predicting that the variant has no impact on splicing (score threshold ≤ 0.10) (BP4).
PM2_Supporting
This variant has an allele frequency of 6.195e-7 (1/1614158 alleles) across gnomAD v4.1.0 which is lower than the Clingen TP53 VCEP threshold (<0.00003) for PM2_Supporting and has no more than one allele per non-bottleneck subpopulation (PM2_Supporting).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
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
BS3
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
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
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
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).
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
ClinGen Terms of Use.
¤ Powered by BCM's Genboree.