NM_000546.6(TP53):c.170A>G (p.Asp57Gly) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 22, 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:: RCV003509905.2

Allele description [Variation Report for NM_000546.6(TP53):c.170A>G (p.Asp57Gly)]

NM_000546.6(TP53):c.170A>G (p.Asp57Gly)

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.170A>G (p.Asp57Gly)

HGVS:

NC_000017.11:g.7676199T>C
NG_017013.2:g.16352A>G
NM_000546.6:c.170A>GMANE SELECT
NM_001126112.3:c.170A>G
NM_001126113.3:c.170A>G
NM_001126114.3:c.170A>G
NM_001126118.2:c.53A>G
NM_001276695.3:c.53A>G
NM_001276696.3:c.53A>G
NM_001276760.3:c.53A>G
NM_001276761.3:c.53A>G
NM_001407262.1:c.170A>G
NM_001407263.1:c.53A>G
NM_001407264.1:c.170A>G
NM_001407265.1:c.53A>G
NM_001407266.1:c.170A>G
NM_001407267.1:c.53A>G
NM_001407268.1:c.170A>G
NM_001407269.1:c.53A>G
NM_001407270.1:c.170A>G
NM_001407271.1:c.53A>G
NP_000537.3:p.Asp57Gly
NP_000537.3:p.Asp57Gly
NP_001119584.1:p.Asp57Gly
NP_001119584.1:p.Asp57Gly
NP_001119585.1:p.Asp57Gly
NP_001119585.1:p.Asp57Gly
NP_001119586.1:p.Asp57Gly
NP_001119586.1:p.Asp57Gly
NP_001119590.1:p.Asp18Gly
NP_001119590.1:p.Asp18Gly
NP_001263624.1:p.Asp18Gly
NP_001263625.1:p.Asp18Gly
NP_001263689.1:p.Asp18Gly
NP_001263690.1:p.Asp18Gly
NP_001394191.1:p.Asp57Gly
NP_001394192.1:p.Asp18Gly
NP_001394193.1:p.Asp57Gly
NP_001394194.1:p.Asp18Gly
NP_001394195.1:p.Asp57Gly
NP_001394196.1:p.Asp18Gly
NP_001394197.1:p.Asp57Gly
NP_001394198.1:p.Asp18Gly
NP_001394199.1:p.Asp57Gly
NP_001394200.1:p.Asp18Gly
LRG_321t1:c.170A>G
LRG_321t2:c.170A>G
LRG_321t3:c.170A>G
LRG_321t4:c.170A>G
LRG_321t8:c.53A>G
LRG_321:g.16352A>G
LRG_321:p.Asp57Gly
LRG_321p1:p.Asp57Gly
LRG_321p3:p.Asp57Gly
LRG_321p4:p.Asp57Gly
LRG_321p8:p.Asp18Gly
NC_000017.10:g.7579517T>C
NM_000546.5:c.170A>G
NM_001126112.2:c.170A>G
NM_001126113.2:c.170A>G
NM_001126114.2:c.170A>G
NM_001126118.1:c.53A>G
NR_176326.1:n.312A>G

Protein change:

D18G

Molecular consequence:

NM_000546.6:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.53A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176326.1:n.312A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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cytochrome c oxidase subunit 1 (mitochondrion) [Dinoderus minutus]
cytochrome c oxidase subunit 1 (mitochondrion) [Dinoderus minutus]
gi|1178767924|gb|ARH53806.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004245651	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 22, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004245651

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 22, 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

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

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004245651.1

#	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 aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 57 of the TP53 protein (p.Asp57Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TP53-related conditions. 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 with a negative predictive value of 97.5%. 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: Nov 10, 2024

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