NM_000546.6(TP53):c.188C>T (p.Ala63Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 22, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000161018.13

Allele description [Variation Report for NM_000546.6(TP53):c.188C>T (p.Ala63Val)]

NM_000546.6(TP53):c.188C>T (p.Ala63Val)

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.188C>T (p.Ala63Val)

Other names:

p.A63V:GCT>GTT

HGVS:

NC_000017.11:g.7676181G>A
NG_017013.2:g.16370C>T
NM_000546.6:c.188C>TMANE SELECT
NM_001126112.3:c.188C>T
NM_001126113.3:c.188C>T
NM_001126114.3:c.188C>T
NM_001126118.2:c.71C>T
NM_001276695.3:c.71C>T
NM_001276696.3:c.71C>T
NM_001276760.3:c.71C>T
NM_001276761.3:c.71C>T
NP_000537.3:p.Ala63Val
NP_000537.3:p.Ala63Val
NP_001119584.1:p.Ala63Val
NP_001119585.1:p.Ala63Val
NP_001119586.1:p.Ala63Val
NP_001119590.1:p.Ala24Val
NP_001263624.1:p.Ala24Val
NP_001263625.1:p.Ala24Val
NP_001263689.1:p.Ala24Val
NP_001263690.1:p.Ala24Val
LRG_321t1:c.188C>T
LRG_321t2:c.188C>T
LRG_321:g.16370C>T
LRG_321p1:p.Ala63Val
NC_000017.10:g.7579499G>A
NM_000546.4:c.188C>T
NM_000546.5:c.188C>T
NM_001126112.2(TP53):c.188C>T
P04637:p.Ala63Val
p.A63V

Protein change:

A24V

Links:

UniProtKB: P04637#VAR_044590; dbSNP: rs372201428

NCBI 1000 Genomes Browser:

rs372201428

Molecular consequence:

NM_000546.6:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.71C>T - 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
SCV000215136	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Oct 22, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12826609, 30224644 Citation Link,
SCV000908800	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 14, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000215136

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Oct 22, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000908800

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 14, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 (3)

Details of each submission

From Ambry Genetics, SCV000215136.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000908800.2

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

#	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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