NM_000546.6(TP53):c.773A>C (p.Glu258Ala) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 12, 2019
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:: RCV001001211.9

Allele description [Variation Report for NM_000546.6(TP53):c.773A>C (p.Glu258Ala)]

NM_000546.6(TP53):c.773A>C (p.Glu258Ala)

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.773A>C (p.Glu258Ala)

HGVS:

NC_000017.11:g.7674190T>G
NG_017013.2:g.18361A>C
NM_000546.6:c.773A>CMANE SELECT
NM_001126112.3:c.773A>C
NM_001126113.3:c.773A>C
NM_001126114.3:c.773A>C
NM_001126115.2:c.377A>C
NM_001126116.2:c.377A>C
NM_001126117.2:c.377A>C
NM_001126118.2:c.656A>C
NM_001276695.3:c.656A>C
NM_001276696.3:c.656A>C
NM_001276697.3:c.296A>C
NM_001276698.3:c.296A>C
NM_001276699.3:c.296A>C
NM_001276760.3:c.656A>C
NM_001276761.3:c.656A>C
NP_000537.3:p.Glu258Ala
NP_000537.3:p.Glu258Ala
NP_001119584.1:p.Glu258Ala
NP_001119585.1:p.Glu258Ala
NP_001119586.1:p.Glu258Ala
NP_001119587.1:p.Glu126Ala
NP_001119588.1:p.Glu126Ala
NP_001119589.1:p.Glu126Ala
NP_001119590.1:p.Glu219Ala
NP_001263624.1:p.Glu219Ala
NP_001263625.1:p.Glu219Ala
NP_001263626.1:p.Glu99Ala
NP_001263627.1:p.Glu99Ala
NP_001263628.1:p.Glu99Ala
NP_001263689.1:p.Glu219Ala
NP_001263690.1:p.Glu219Ala
LRG_321t1:c.773A>C
LRG_321:g.18361A>C
LRG_321p1:p.Glu258Ala
NC_000017.10:g.7577508T>G
NM_000546.5:c.773A>C

Protein change:

E126A

Links:

dbSNP: rs1060501201

NCBI 1000 Genomes Browser:

rs1060501201

Molecular consequence:

NM_000546.6:c.773A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.773A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.773A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.773A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.377A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.377A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.377A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.656A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.656A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.656A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.296A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.296A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.296A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.656A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.656A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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SRS9150801 (1)
SRA
Mus musculus 3-oxoacyl-ACP synthase, mitochondrial, mRNA (cDNA clone MGC:144806 ...
Mus musculus 3-oxoacyl-ACP synthase, mitochondrial, mRNA (cDNA clone MGC:144806 IMAGE:40106281), complete cds
gi|111054912|gb|BC119793.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001158372	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Apr 12, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001158372

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Apr 12, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158372.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The TP53 c.773A>C; p.Glu258Ala variant, to our knowledge, has not been reported in the germline of an individual with Li-Fraumeni syndrome (LFS), but has been published in tumor samples (Chen 2006, Verdijk 2010). However, another variant in the same codon, p.Glu258Lys, has been published in families with LFS (Monti 2007, Masciari 2011) and this variant may have altered function (Malcikova 2010, Monti 2011). The c.773A>C; p.Glu258Ala variant is described in the ClinVar database (Variation ID: 458563) but is absent from the general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The amino acid at this position is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Due to limited information, the clinical significance of the variant is uncertain at this time. References: Chen YJ et al. Association of mutant TP53 with alternative lengthening of telomeres and favorable prognosis in glioma. Cancer Res. 2006 Jul 1;66(13):6473-6. Malcikova J et al. Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation. Biol Chem. 2010 Feb-Mar;391(2-3):197-205. Masciari S et al. Gastric cancer in individuals with Li-Fraumeni syndrome. Genet Med. 2011 Jul;13(7):651-7. Monti P et al. Transcriptional functionality of germ line p53 mutants influences cancer phenotype. Clin Cancer Res. 2007 Jul 1;13(13):3789-95. Monti P et al. Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. Mol Cancer Res. 2011 Mar;9(3):271-9 Verdijk RM et al. TP53 mutation analysis of malignant peripheral nerve sheath tumors. J Neuropathol Exp Neurol. 2010 Jan;69(1):16-26.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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