NM_000546.6(TP53):c.28G>A (p.Val10Ile) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Oct 1, 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:: RCV000235217.15

Allele description [Variation Report for NM_000546.6(TP53):c.28G>A (p.Val10Ile)]

NM_000546.6(TP53):c.28G>A (p.Val10Ile)

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.28G>A (p.Val10Ile)

Other names:

p.V10I:GTC>ATC

HGVS:

NC_000017.11:g.7676567C>T
NG_017013.2:g.15984G>A
NM_000546.6:c.28G>AMANE SELECT
NM_001126112.3:c.28G>A
NM_001126113.3:c.28G>A
NM_001126114.3:c.28G>A
NM_001126118.2:c.-207G>A
NM_001276695.3:c.-90G>A
NM_001276696.3:c.-90G>A
NM_001276760.3:c.-90G>A
NM_001276761.3:c.-90G>A
NP_000537.3:p.Val10Ile
NP_000537.3:p.Val10Ile
NP_001119584.1:p.Val10Ile
NP_001119585.1:p.Val10Ile
NP_001119586.1:p.Val10Ile
LRG_321t1:c.28G>A
LRG_321:g.15984G>A
LRG_321p1:p.Val10Ile
NC_000017.10:g.7579885C>T
NM_000546.4:c.28G>A
NM_000546.5(TP53):c.28G>A
NM_000546.5:c.28G>A
P04637:p.Val10Ile
p.V10I

Protein change:

V10I

Links:

UniProtKB: P04637#VAR_044546; dbSNP: rs535274413

NCBI 1000 Genomes Browser:

rs535274413

Molecular consequence:

NM_001126118.2:c.-207G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276695.3:c.-90G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276696.3:c.-90G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276760.3:c.-90G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276761.3:c.-90G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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glycosyltransferase, partial [Arabidopsis thaliana]
glycosyltransferase, partial [Arabidopsis thaliana]
gi|591402306|gb|AHL38880.1|

Protein
txid940221[Organism:noexp] (2)
Nucleotide
txid92536[Organism:noexp] (1466)
Protein
PMC Links for Nucleotide (Select 1519242320) (3)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149626	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Oct 1, 2020)	germline	clinical testing	Citation Link,
SCV000884715	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (Jun 20, 2017)	germline	clinical testing	Citation Link,
SCV005218660	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000149626

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Oct 1, 2020)

germline

clinical testing

Citation Link,

SCV000884715

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(Jun 20, 2017)

germline

clinical testing

Citation Link,

SCV005218660

Breakthrough Genomics, Breakthrough Genomics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign

germline

not provided

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000149626.16

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 19651601, 24811890, 25186627, 30287823, 30840781, 30224644, 33300245)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000884715.1

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

Description

The TP53 c.28G>A;p.Val10Ile variant has been shown to function similarly to wild type in at least some functional studies (Kato 2003, Shiraishi 2004). The variant is listed in the ClinVar database (Variation ID: 127806) and the dbSNP variant database (rs535274413) with an allele frequency of 0.003258 percent (8/245572 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved across species and computational algorithms (Align GVGD, PolyPhen2, SIFT) predict this variant is tolerated, although the amino acid is located in the transactivation domain (Bode 2004). Considering available information, there is insufficient evidence to classify the variant with certainty. If this variant is later determined to be pathogenic, this individual would be at increased risk for development of hereditary cancers (OMIM#191170). References: Bode AM and Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer. 2004 Oct;4(10):793-805. Kato S et al. Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9. Shiraishi K et al. Isolation of temperature-sensitive p53 mutations from a comprehensive missense mutation library. J Biol Chem. 2004 Jan 2;279(1):348-55.

#	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 Breakthrough Genomics, Breakthrough Genomics, SCV005218660.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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