NM_000546.6(TP53):c.373A>G (p.Thr125Ala) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 2015
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:: RCV002349223.2

Allele description [Variation Report for NM_000546.6(TP53):c.373A>G (p.Thr125Ala)]

NM_000546.6(TP53):c.373A>G (p.Thr125Ala)

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.373A>G (p.Thr125Ala)

HGVS:

NC_000017.11:g.7675996T>C
NG_017013.2:g.16555A>G
NM_000546.6:c.373A>GMANE SELECT
NM_001126112.3:c.373A>G
NM_001126113.3:c.373A>G
NM_001126114.3:c.373A>G
NM_001126118.2:c.256A>G
NM_001276695.3:c.256A>G
NM_001276696.3:c.256A>G
NM_001276760.3:c.256A>G
NM_001276761.3:c.256A>G
NM_001407262.1:c.373A>G
NM_001407263.1:c.256A>G
NM_001407264.1:c.373A>G
NM_001407265.1:c.256A>G
NM_001407266.1:c.373A>G
NM_001407267.1:c.256A>G
NM_001407268.1:c.373A>G
NM_001407269.1:c.256A>G
NM_001407270.1:c.373A>G
NM_001407271.1:c.256A>G
NP_000537.3:p.Thr125Ala
NP_000537.3:p.Thr125Ala
NP_001119584.1:p.Thr125Ala
NP_001119584.1:p.Thr125Ala
NP_001119585.1:p.Thr125Ala
NP_001119585.1:p.Thr125Ala
NP_001119586.1:p.Thr125Ala
NP_001119586.1:p.Thr125Ala
NP_001119590.1:p.Thr86Ala
NP_001119590.1:p.Thr86Ala
NP_001263624.1:p.Thr86Ala
NP_001263625.1:p.Thr86Ala
NP_001263689.1:p.Thr86Ala
NP_001263690.1:p.Thr86Ala
NP_001394191.1:p.Thr125Ala
NP_001394192.1:p.Thr86Ala
NP_001394193.1:p.Thr125Ala
NP_001394194.1:p.Thr86Ala
NP_001394195.1:p.Thr125Ala
NP_001394196.1:p.Thr86Ala
NP_001394197.1:p.Thr125Ala
NP_001394198.1:p.Thr86Ala
NP_001394199.1:p.Thr125Ala
NP_001394200.1:p.Thr86Ala
LRG_321t1:c.373A>G
LRG_321t2:c.373A>G
LRG_321t3:c.373A>G
LRG_321t4:c.373A>G
LRG_321t8:c.256A>G
LRG_321:g.16555A>G
LRG_321:p.Thr125Ala
LRG_321p1:p.Thr125Ala
LRG_321p3:p.Thr125Ala
LRG_321p4:p.Thr125Ala
LRG_321p8:p.Thr86Ala
NC_000017.10:g.7579314T>C
NM_000546.4:c.373A>G
NM_000546.5:c.373A>G
NM_001126112.2:c.373A>G
NM_001126113.2:c.373A>G
NM_001126114.2:c.373A>G
NM_001126118.1:c.256A>G
NR_176326.1:n.515A>G

Protein change:

T125A

Molecular consequence:

NM_000546.6:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.256A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.373A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.256A>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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E3 ubiquitin-protein ligase Os04g0590900 [Cucumis sativus]
E3 ubiquitin-protein ligase Os04g0590900 [Cucumis sativus]
gi|778687904|ref|XP_011652647.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002621216	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 22, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002621216

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 22, 2015)

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 Ambry Genetics, SCV002621216.2

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

Description

The p.T125A variant (also known as c.373A>G), located in coding exon 3 of the TP53 gene, results from an A to G substitution at nucleotide position 373. The threonine at codon 125 is replaced by alanine, an amino acid with similar properties. This alteration is in the DNA binding domain of the TP53 protein and is reported to have partial loss of transactivation capacity; it has been reported as a somatic mutation once but not as a germline mutation by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum Mutat. 2007 Jun;28(6):622-9; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). This alteration has been shown to reduce DNA binding activity (Zupnick A and Prives C. J Biol Chem. 2006 Jul 21;281(29):20464-73). 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.T125A 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

Last Updated: May 1, 2024

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