NM_000546.6(TP53):c.1073A>T (p.Glu358Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Jul 13, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000219841.11

Allele description [Variation Report for NM_000546.6(TP53):c.1073A>T (p.Glu358Val)]

NM_000546.6(TP53):c.1073A>T (p.Glu358Val)

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.1073A>T (p.Glu358Val)

HGVS:

NC_000017.11:g.7670636T>A
NG_017013.2:g.21915A>T
NM_000546.6:c.1073A>TMANE SELECT
NM_001126112.3:c.1073A>T
NM_001126113.3:c.*92A>T
NM_001126114.3:c.*180A>T
NM_001126115.2:c.677A>T
NM_001126116.2:c.*180A>T
NM_001126117.2:c.*92A>T
NM_001126118.2:c.956A>T
NM_001276695.3:c.*92A>T
NM_001276696.3:c.*180A>T
NM_001276697.3:c.596A>T
NM_001276698.3:c.*180A>T
NM_001276699.3:c.*92A>T
NM_001276760.3:c.956A>T
NM_001276761.3:c.956A>T
NP_000537.3:p.Glu358Val
NP_000537.3:p.Glu358Val
NP_001119584.1:p.Glu358Val
NP_001119587.1:p.Glu226Val
NP_001119590.1:p.Glu319Val
NP_001263626.1:p.Glu199Val
NP_001263689.1:p.Glu319Val
NP_001263690.1:p.Glu319Val
LRG_321t1:c.1073A>T
LRG_321:g.21915A>T
LRG_321p1:p.Glu358Val
NC_000017.10:g.7573954T>A
NM_000546.4:c.1073A>T
NM_000546.5:c.1073A>T

Protein change:

E199V

Links:

dbSNP: rs773553186

NCBI 1000 Genomes Browser:

rs773553186

Molecular consequence:

NM_001126113.3:c.*92A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126114.3:c.*180A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126116.2:c.*180A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001126117.2:c.*92A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276695.3:c.*92A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276696.3:c.*180A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276698.3:c.*180A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001276699.3:c.*92A>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000546.6:c.1073A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.1073A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.677A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.956A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.596A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.956A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.956A>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
SCV000274118	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 9, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28724667, 28861920, 29470806 Citation Link,
SCV000904076	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 13, 2020)	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

SCV000274118

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Sep 9, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000904076

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 13, 2020)

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

Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.

Sun J, Meng H, Yao L, Lv M, Bai J, Zhang J, Wang L, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, Xie Y.

Clin Cancer Res. 2017 Oct 15;23(20):6113-6119. doi: 10.1158/1078-0432.CCR-16-3227. Epub 2017 Jul 19.

PubMed [citation]

PMID:: 28724667

Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.

de Andrade KC, Mirabello L, Stewart DR, Karlins E, Koster R, Wang M, Gapstur SM, Gaudet MM, Freedman ND, Landi MT, Lemonnier N, Hainaut P, Savage SA, Achatz MI.

Hum Mutat. 2017 Dec;38(12):1723-1730. doi: 10.1002/humu.23320. Epub 2017 Sep 21.

PubMed [citation]

PMID:: 28861920
PMCID:: PMC6858060

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000274118.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

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, SCV000904076.2

#	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: May 1, 2024

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