NM_000546.6(TP53):c.8A>G (p.Glu3Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 18, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000167456.5

Allele description [Variation Report for NM_000546.6(TP53):c.8A>G (p.Glu3Gly)]

NM_000546.6(TP53):c.8A>G (p.Glu3Gly)

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.8A>G (p.Glu3Gly)

HGVS:

NC_000017.11:g.7676587T>C
NG_017013.2:g.15964A>G
NM_000546.6:c.8A>GMANE SELECT
NM_001126112.3:c.8A>G
NM_001126113.3:c.8A>G
NM_001126114.3:c.8A>G
NM_001126118.2:c.-227A>G
NM_001276695.3:c.-110A>G
NM_001276696.3:c.-110A>G
NM_001276760.3:c.-110A>G
NM_001276761.3:c.-110A>G
NP_000537.3:p.Glu3Gly
NP_000537.3:p.Glu3Gly
NP_001119584.1:p.Glu3Gly
NP_001119585.1:p.Glu3Gly
NP_001119586.1:p.Glu3Gly
LRG_321t1:c.8A>G
LRG_321:g.15964A>G
LRG_321p1:p.Glu3Gly
NC_000017.10:g.7579905T>C
NM_000546.4:c.8A>G
NM_000546.5:c.8A>G
p.E3G

Protein change:

E3G

Links:

dbSNP: rs786203938

NCBI 1000 Genomes Browser:

rs786203938

Molecular consequence:

NM_001126118.2:c.-227A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-110A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-110A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-110A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-110A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.8A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.8A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.8A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.8A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218312	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 23, 2014)	germline	clinical testing	Citation Link,
SCV002582189	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000218312

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 23, 2014)

germline

clinical testing

Citation Link,

SCV002582189

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000218312.7

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

Description

The p.E3G variant (also known as c.8A>G), located in coding exon 1 of the TP53 gene, results from an A to G substitution at nucleotide position 8. The glutamic acid at codon 3 is replaced by glycine, an amino acid with similar properties. Functional studies have shown this alteration to be capable of transcriptional activation in yeast based assays (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,503 samples (13,006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 87,000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.E3G remains unclear.

#	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

From Genome-Nilou Lab, SCV002582189.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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