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NM_000546.6(TP53):c.257C>T (p.Ala86Val) AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 7, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000810093.7

Allele description

NM_000546.6(TP53):c.257C>T (p.Ala86Val)

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.257C>T (p.Ala86Val)
HGVS:
  • NC_000017.11:g.7676112G>A
  • NG_017013.2:g.16439C>T
  • NM_000546.6:c.257C>TMANE SELECT
  • NM_001126112.3:c.257C>T
  • NM_001126113.3:c.257C>T
  • NM_001126114.3:c.257C>T
  • NM_001126118.2:c.140C>T
  • NM_001276695.3:c.140C>T
  • NM_001276696.3:c.140C>T
  • NM_001276760.3:c.140C>T
  • NM_001276761.3:c.140C>T
  • NP_000537.3:p.Ala86Val
  • NP_000537.3:p.Ala86Val
  • NP_001119584.1:p.Ala86Val
  • NP_001119585.1:p.Ala86Val
  • NP_001119586.1:p.Ala86Val
  • NP_001119590.1:p.Ala47Val
  • NP_001263624.1:p.Ala47Val
  • NP_001263625.1:p.Ala47Val
  • NP_001263689.1:p.Ala47Val
  • NP_001263690.1:p.Ala47Val
  • LRG_321t1:c.257C>T
  • LRG_321:g.16439C>T
  • LRG_321p1:p.Ala86Val
  • NC_000017.10:g.7579430G>A
  • NM_000546.4:c.257C>T
  • NM_000546.5:c.257C>T
Protein change:
A47V
Links:
dbSNP: rs1597374264
NCBI 1000 Genomes Browser:
rs1597374264
Molecular consequence:
  • NM_000546.6:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126112.3:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126113.3:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126114.3:c.257C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001126118.2:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276695.3:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276696.3:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276760.3:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001276761.3:c.140C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000950281Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 7, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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

Network effect of Wt-mutant p53 interactions and implications on p53 gene therapy.

Ji X, Ma L, Huang Q, Li Z, Zhao J, Huang W, Ma B, Yu L.

Curr Pharm Des. 2014;20(8):1259-67.

PubMed [citation]
PMID:
23713777
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000950281.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 86 of the TP53 protein (p.Ala86Val). This missense change has been observed in individual(s) with hepatocellular carcinoma (PMID: 23713777). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609, 23713777). Advanced modeling of experimental studies (such as gene expression, population dynamics, functional pathways, and cell-cycle effects in cell culture) performed at Invitae indicates that this missense variant is not expected to disrupt TP53 protein function. ClinVar contains an entry for this variant (Variation ID: 654187).

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

Last Updated: May 1, 2024