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NM_000546.6(TP53):c.37C>T (p.Pro13Ser) AND Li-Fraumeni syndrome 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 27, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001724014.4

Allele description [Variation Report for NM_000546.6(TP53):c.37C>T (p.Pro13Ser)]

NM_000546.6(TP53):c.37C>T (p.Pro13Ser)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.6(TP53):c.37C>T (p.Pro13Ser)
Other names:
NM_000546.5(TP53):c.37C>T; p.Pro13Ser
HGVS:
  • NC_000017.11:g.7676558G>A
  • NG_017013.2:g.15993C>T
  • NM_000546.6:c.37C>TMANE SELECT
  • NM_001126112.3:c.37C>T
  • NM_001126113.3:c.37C>T
  • NM_001126114.3:c.37C>T
  • NM_001126118.2:c.-198C>T
  • NM_001276695.3:c.-81C>T
  • NM_001276696.3:c.-81C>T
  • NM_001276760.3:c.-81C>T
  • NM_001276761.3:c.-81C>T
  • NP_000537.3:p.Pro13Ser
  • NP_000537.3:p.Pro13Ser
  • NP_001119584.1:p.Pro13Ser
  • NP_001119585.1:p.Pro13Ser
  • NP_001119586.1:p.Pro13Ser
  • LRG_321t1:c.37C>T
  • LRG_321:g.15993C>T
  • LRG_321p1:p.Pro13Ser
  • NC_000017.10:g.7579876G>A
  • NM_000546.4:c.37C>T
  • NM_000546.5:c.37C>T
Protein change:
P13S
Links:
dbSNP: rs1060501208
NCBI 1000 Genomes Browser:
rs1060501208
Molecular consequence:
  • NM_001126118.2:c.-198C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276695.3:c.-81C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276696.3:c.-81C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276760.3:c.-81C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001276761.3:c.-81C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000546.6:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Identifiers:
Gene: 553989; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001949913ClinGen TP53 Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen TP53 ACMG Specifications v1-2)		Uncertain significance
(Jun 27, 2022) 		germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.

Kato S, Han SY, Liu W, Otsuka K, Shibata H, Kanamaru R, Ishioka C.

Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Epub 2003 Jun 25.

PubMed [citation]
PMID:
12826609
PMCID:
PMC166245

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]
PMID:
30224644
PMCID:
PMC6168352

Details of each submission

From ClinGen TP53 Variant Curation Expert Panel, ClinGen, SCV001949913.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

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 < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). This variant has been reported in 2 probands meeting Revised Chompret criteria (PS4_Supporting; internal laboratory contributor). The TP53 VCEP allows classification of a variant as Likely Benign with two supporting benign evidence codes if there is only a single supporting pathogenic code. However, the group did not feel a classification of Likely Benign was appropriate for this variant at this time given that the BayesDel score is just below the VCEP threshold and considering the phenotypes reported in the families meeting Chompret criteria. In summary, the clinical significance of TP53 c.37C>T (p.Pro13Ser) is uncertain for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BP4, PS4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025