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

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Interpretation:
Likely benign​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
7 (Most recent: Jun 18, 2021)
Last evaluated:
Apr 12, 2021
Accession:
VCV000182922.11
Variation ID:
182922
Description:
single nucleotide variant
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NM_000546.5(TP53):c.188C>T (p.Ala63Val)

Allele ID
181027
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7676181 (GRCh38) GRCh38 UCSC
17: 7579499 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7579499G>A
NC_000017.11:g.7676181G>A
NM_000546.5:c.188C>T NP_000537.3:p.Ala63Val missense
... more HGVS
Protein change
A24V, A63V
Other names
p.A63V:GCT>GTT
Canonical SPDI
NC_000017.11:7676180:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Links
ClinGen: CA000063
UniProtKB: P04637#VAR_044590
dbSNP: rs372201428
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 2 reviewed by expert panel Apr 12, 2021 RCV000663264.2
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Mar 14, 2019 RCV000161018.7
Uncertain significance 1 criteria provided, single submitter Nov 2, 2017 RCV000213047.2
Uncertain significance 1 criteria provided, single submitter Oct 30, 2020 RCV000467874.6
Uncertain significance 1 criteria provided, single submitter Oct 22, 2020 RCV001264516.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TP53 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2205 2268

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Apr 12, 2021)
reviewed by expert panel
Method: curation
Li-Fraumeni syndrome 1
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen TP53 Variant Curation Expert Panel,ClinGen
FDA Recognized Database
Accession: SCV001737942.1
Submitted: (Jun 18, 2021)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
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 … (more)
Uncertain significance
(May 14, 2018)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome 1
Allele origin: unknown
Counsyl
Accession: SCV000786495.2
Submitted: (Jun 20, 2018)
Evidence details
Publications
PubMed (3)
Uncertain significance
(Nov 02, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000211735.12
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted TP53 c.188C>T at the cDNA level, p.Ala63Val (A63V) at the protein level, and results in the change of an Alanine to … (more)
Uncertain significance
(Mar 14, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000908800.2
Submitted: (May 19, 2020)
Evidence details
Uncertain significance
(Oct 22, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001442710.1
Submitted: (Nov 10, 2020)
Evidence details
Publications
PubMed (3)
Comment:
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 … (more)
Uncertain significance
(Sep 06, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000215136.5
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The p.A63V variant (also known as c.188C>T), located in coding exon 3 of the TP53 gene, results from a C to T substitution at nucleotide … (more)
Uncertain significance
(Oct 30, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV000545312.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces alanine with valine at codon 63 of the TP53 protein (p.Ala63Val). The alanine residue is moderately conserved and there is a … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis. de Andrade KC Human mutation 2019 PMID: 30352134
Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history. de Andrade KC Human mutation 2017 PMID: 28861920
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
The (1-63) region of the p53 transactivation domain aggregates in vitro into cytotoxic amyloid assemblies. Rigacci S Biophysical journal 2008 PMID: 18199664
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Kato S Proceedings of the National Academy of Sciences of the United States of America 2003 PMID: 12826609
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/ef9d90c6-8b7a-4989-9f0f-7bd7f52113b0 - - - -

Text-mined citations for rs372201428...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 23, 2021