NM_000546.5(TP53):c.188C>T (p.Ala63Val) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Oct 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001264516.1

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)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001442710Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Oct 22, 2020)
germlineclinical testing

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

Citation Link

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

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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442710.1

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

Description

Variant summary: TP53 c.188C>T (p.Ala63Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251036 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.188C>T in individuals affected with Li-Fraumeni Syndrome has been reported. Several publications however report this variant as likely benign among variants detected in the gnomAD/ExAC datasets (example, de Andrade_2017, de Andrade_2019). At least one publication reports experimental evidence evaluating an impact on protein function (example, Kato_2003). These results showed no damaging effect of this variant based on overall transcription activity (TA) on eight different promoters as measured in yeast assays. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance, some citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jun 23, 2021

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