NM_000546.6(TP53):c.515T>A (p.Val172Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 11, 2017
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:: RCV002337102.2

Allele description [Variation Report for NM_000546.6(TP53):c.515T>A (p.Val172Asp)]

NM_000546.6(TP53):c.515T>A (p.Val172Asp)

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.515T>A (p.Val172Asp)

HGVS:

NC_000017.11:g.7675097A>T
NG_017013.2:g.17454T>A
NM_000546.6:c.515T>AMANE SELECT
NM_001126112.3:c.515T>A
NM_001126113.3:c.515T>A
NM_001126114.3:c.515T>A
NM_001126115.2:c.119T>A
NM_001126116.2:c.119T>A
NM_001126117.2:c.119T>A
NM_001126118.2:c.398T>A
NM_001276695.3:c.398T>A
NM_001276696.3:c.398T>A
NM_001276697.3:c.38T>A
NM_001276698.3:c.38T>A
NM_001276699.3:c.38T>A
NM_001276760.3:c.398T>A
NM_001276761.3:c.398T>A
NP_000537.3:p.Val172Asp
NP_001119584.1:p.Val172Asp
NP_001119585.1:p.Val172Asp
NP_001119586.1:p.Val172Asp
NP_001119587.1:p.Val40Asp
NP_001119588.1:p.Val40Asp
NP_001119589.1:p.Val40Asp
NP_001119590.1:p.Val133Asp
NP_001263624.1:p.Val133Asp
NP_001263625.1:p.Val133Asp
NP_001263626.1:p.Val13Asp
NP_001263627.1:p.Val13Asp
NP_001263628.1:p.Val13Asp
NP_001263689.1:p.Val133Asp
NP_001263690.1:p.Val133Asp
LRG_321t1:c.515T>A
LRG_321:g.17454T>A
NC_000017.10:g.7578415A>T
NM_000546.4:c.515T>A
NM_000546.5:c.515T>A

Protein change:

V133D

Links:

dbSNP: rs1131691021

NCBI 1000 Genomes Browser:

rs1131691021

Molecular consequence:

NM_000546.6:c.515T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.515T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.515T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.515T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.119T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.119T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.119T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.398T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.398T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.398T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.38T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.38T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.38T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.398T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.398T>A - 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
SCV002641346	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Oct 11, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002641346

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Oct 11, 2017)

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, SCV002641346.2

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

Description

The p.V172D variant (also known as c.515T>A), located in coding exon 4 of the TP53 gene, results from a T to A substitution at nucleotide position 515. The valine at codon 172 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This variant is located in the functionally critical DNA binding domain and showed loss of transactivation capacity in comparison to wild type in a yeast-based functional assay (IARC TP53 database; Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9). A different alteration at this codon, p.V172F, was detected in a patient meeting classic Li-Fraumeni syndrome (LFS) criteria (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Sep 29, 2024

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