NM_000546.5(TP53):c.188C>T (p.Ala63Val) AND Li-Fraumeni syndrome 1

Clinical significance:Likely benign (Last evaluated: Apr 12, 2021)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000663264.2

Allele description [Variation Report for NM_000546.5(TP53):c.188C>T (p.Ala63Val)]

NM_000546.5(TP53):c.188C>T (p.Ala63Val)

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.188C>T (p.Ala63Val)
Other names:
p.A63V:GCT>GTT
HGVS:
  • NC_000017.11:g.7676181G>A
  • NG_017013.2:g.16370C>T
  • NM_000546.5:c.188C>T
  • NM_001126112.2:c.188C>T
  • NM_001126113.2:c.188C>T
  • NM_001126114.2:c.188C>T
  • NM_001126118.1:c.71C>T
  • NM_001276695.2:c.71C>T
  • NM_001276696.2:c.71C>T
  • NM_001276760.2:c.71C>T
  • NM_001276761.2:c.71C>T
  • NP_000537.3:p.Ala63Val
  • NP_001119584.1:p.Ala63Val
  • NP_001119585.1:p.Ala63Val
  • NP_001119586.1:p.Ala63Val
  • NP_001119590.1:p.Ala24Val
  • NP_001263624.1:p.Ala24Val
  • NP_001263625.1:p.Ala24Val
  • NP_001263689.1:p.Ala24Val
  • NP_001263690.1:p.Ala24Val
  • LRG_321t1:c.188C>T
  • LRG_321t2:c.188C>T
  • LRG_321t3:c.188C>T
  • LRG_321t4:c.188C>T
  • LRG_321t8:c.71C>T
  • LRG_321:g.16370C>T
  • LRG_321:p.Ala63Val
  • LRG_321p1:p.Ala63Val
  • LRG_321p3:p.Ala63Val
  • LRG_321p4:p.Ala63Val
  • LRG_321p8:p.Ala24Val
  • NC_000017.10:g.7579499G>A
  • NM_000546.4:c.188C>T
  • NM_001126112.2(TP53):c.188C>T
  • P04637:p.Ala63Val
  • p.A63V
Protein change:
A24V
Links:
UniProtKB: P04637#VAR_044590; dbSNP: rs372201428
NCBI 1000 Genomes Browser:
rs372201428
Molecular consequence:
  • NM_000546.5:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.2:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.1:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome 1 (LFS)
Synonyms:
Li-Fraumeni syndrome 3
Identifiers:
Gene: 553989; MONDO: MONDO:0007903; MedGen: C1835398; Orphanet: 524; OMIM: 151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000786495Counsylcriteria provided, single submitter
Uncertain significance
(May 14, 2018)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf,

Citation Link,

SCV001737942ClinGen TP53 Variant Curation Expert Panel,ClinGenreviewed by expert panel
Likely benign
(Apr 12, 2021)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

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

Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.

de Andrade KC, Mirabello L, Stewart DR, Karlins E, Koster R, Wang M, Gapstur SM, Gaudet MM, Freedman ND, Landi MT, Lemonnier N, Hainaut P, Savage SA, Achatz MI.

Hum Mutat. 2017 Dec;38(12):1723-1730. doi: 10.1002/humu.23320. Epub 2017 Sep 21.

PubMed [citation]
PMID:
28861920
PMCID:
PMC6858060
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000786495.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen TP53 Variant Curation Expert Panel,ClinGen, SCV001737942.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Transactivation assays show [retained/supertransactivation] 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 been observed in 2 60+ year old females without a cancer diagnosis (BS2_Supporting: internal laboratory contributor (SCV000545312.6). This variant has a BayesDel score < 0.16 and Align GVGD (Zebrafish) is Class C0 (BP4). In summary, TP53 c.188C>T (p.Ala63Val) meets criteria to be classified as likely benign for Li-Fraumeni syndrome. ACMG/AMP criteria applied, as specified by the TP53 Variant Curation Expert Panel: BS3, BS2, BP4.

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

Last Updated: Jun 23, 2021

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