NM_000546.6(TP53):c.7G>A (p.Glu3Lys) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 10, 2023
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:: RCV001064070.6

Allele description [Variation Report for NM_000546.6(TP53):c.7G>A (p.Glu3Lys)]

NM_000546.6(TP53):c.7G>A (p.Glu3Lys)

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.7G>A (p.Glu3Lys)

HGVS:

NC_000017.11:g.7676588C>T
NG_017013.2:g.15963G>A
NM_000546.6:c.7G>AMANE SELECT
NM_001126112.3:c.7G>A
NM_001126113.3:c.7G>A
NM_001126114.3:c.7G>A
NM_001126118.2:c.-228G>A
NM_001276695.3:c.-111G>A
NM_001276696.3:c.-111G>A
NM_001276760.3:c.-111G>A
NM_001276761.3:c.-111G>A
NP_000537.3:p.Glu3Lys
NP_001119584.1:p.Glu3Lys
NP_001119585.1:p.Glu3Lys
NP_001119586.1:p.Glu3Lys
LRG_321t1:c.7G>A
LRG_321:g.15963G>A
NC_000017.10:g.7579906C>T
NM_000546.4:c.7G>A
NM_000546.5:c.7G>A

Protein change:

E3K

Links:

dbSNP: rs2073524362

NCBI 1000 Genomes Browser:

rs2073524362

Molecular consequence:

NM_001126118.2:c.-228G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-111G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-111G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-111G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-111G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.7G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.7G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.7G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.7G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001228946	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 10, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29979965, 30224644, 12826609, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001228946

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 10, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Citations

PubMed

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

Mutational processes shape the landscape of TP53 mutations in human cancer.

Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, et al.

Nat Genet. 2018 Oct;50(10):1381-1387. doi: 10.1038/s41588-018-0204-y. Epub 2018 Sep 17.

PubMed [citation]

PMID:: 30224644
PMCID:: PMC6168352

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001228946.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 3 of the TP53 protein (p.Glu3Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 858236). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is not expected to disrupt TP53 function. Experimental studies have shown that this missense change does not substantially affect TP53 function (PMID: 12826609). 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.

#	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: May 1, 2024

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