NM_000546.6(TP53):c.716A>C (p.Asn239Thr) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 9, 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:: RCV000633336.10

Allele description [Variation Report for NM_000546.6(TP53):c.716A>C (p.Asn239Thr)]

NM_000546.6(TP53):c.716A>C (p.Asn239Thr)

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.716A>C (p.Asn239Thr)

HGVS:

NC_000017.11:g.7674247T>G
NG_017013.2:g.18304A>C
NM_000546.6:c.716A>CMANE SELECT
NM_001126112.3:c.716A>C
NM_001126113.3:c.716A>C
NM_001126114.3:c.716A>C
NM_001126115.2:c.320A>C
NM_001126116.2:c.320A>C
NM_001126117.2:c.320A>C
NM_001126118.2:c.599A>C
NM_001276695.3:c.599A>C
NM_001276696.3:c.599A>C
NM_001276697.3:c.239A>C
NM_001276698.3:c.239A>C
NM_001276699.3:c.239A>C
NM_001276760.3:c.599A>C
NM_001276761.3:c.599A>C
NP_000537.3:p.Asn239Thr
NP_000537.3:p.Asn239Thr
NP_001119584.1:p.Asn239Thr
NP_001119585.1:p.Asn239Thr
NP_001119586.1:p.Asn239Thr
NP_001119587.1:p.Asn107Thr
NP_001119588.1:p.Asn107Thr
NP_001119589.1:p.Asn107Thr
NP_001119590.1:p.Asn200Thr
NP_001263624.1:p.Asn200Thr
NP_001263625.1:p.Asn200Thr
NP_001263626.1:p.Asn80Thr
NP_001263627.1:p.Asn80Thr
NP_001263628.1:p.Asn80Thr
NP_001263689.1:p.Asn200Thr
NP_001263690.1:p.Asn200Thr
LRG_321t1:c.716A>C
LRG_321:g.18304A>C
LRG_321p1:p.Asn239Thr
NC_000017.10:g.7577565T>G
NM_000546.4:c.716A>C
NM_000546.5:c.716A>C

Protein change:

N107T

Links:

dbSNP: rs1057519999

NCBI 1000 Genomes Browser:

rs1057519999

Molecular consequence:

NM_000546.6:c.716A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.716A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.716A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.716A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.320A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.320A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.320A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.599A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.599A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.599A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.239A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.599A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.599A>C - 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
SCV000754558	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 9, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20407015, 12826609, 29979965, 30224644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754558

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 9, 2023)

germline

clinical testing

PubMed (5)
[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

Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation.

Jordan JJ, Inga A, Conway K, Edmiston S, Carey LA, Wu L, Resnick MA.

Mol Cancer Res. 2010 May;8(5):701-16. doi: 10.1158/1541-7786.MCR-09-0442. Epub 2010 Apr 20.

PubMed [citation]

PMID:: 20407015
PMCID:: PMC2873663

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754558.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 20407015). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 376638). This variant has not been reported in the literature in individuals affected with TP53-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 239 of the TP53 protein (p.Asn239Thr).

#	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: Feb 25, 2025

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