NM_000546.6(TP53):c.168A>G (p.Glu56=) AND not provided

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Aug 3, 2020
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:: RCV000198234.10

Allele description [Variation Report for NM_000546.6(TP53):c.168A>G (p.Glu56=)]

NM_000546.6(TP53):c.168A>G (p.Glu56=)

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.168A>G (p.Glu56=)

HGVS:

NC_000017.11:g.7676201T>C
NG_017013.2:g.16350A>G
NM_000546.6:c.168A>GMANE SELECT
NM_001126112.3:c.168A>G
NM_001126113.3:c.168A>G
NM_001126114.3:c.168A>G
NM_001126118.2:c.51A>G
NM_001276695.3:c.51A>G
NM_001276696.3:c.51A>G
NM_001276760.3:c.51A>G
NM_001276761.3:c.51A>G
NP_000537.3:p.Glu56=
NP_000537.3:p.Glu56=
NP_001119584.1:p.Glu56=
NP_001119585.1:p.Glu56=
NP_001119586.1:p.Glu56=
NP_001119590.1:p.Glu17=
NP_001263624.1:p.Glu17=
NP_001263625.1:p.Glu17=
NP_001263689.1:p.Glu17=
NP_001263690.1:p.Glu17=
LRG_321t1:c.168A>G
LRG_321:g.16350A>G
LRG_321p1:p.Glu56=
NC_000017.10:g.7579519T>C
NM_000546.4:c.168A>G
NM_000546.5:c.168A>G

Links:

dbSNP: rs574255227

NCBI 1000 Genomes Browser:

rs574255227

Molecular consequence:

NM_000546.6:c.168A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126112.3:c.168A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126113.3:c.168A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126114.3:c.168A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001126118.2:c.51A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276695.3:c.51A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276696.3:c.51A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276760.3:c.51A>G - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001276761.3:c.51A>G - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001469317	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Aug 3, 2020)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27297285, 26467025
SCV001551585	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Likely benign	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001469317

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Aug 3, 2020)

unknown

clinical testing

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

SCV001551585

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Likely benign

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Super-Transactivation TP53 Variant in the Germline of a Family with Li-Fraumeni Syndrome.

Id Said B, Kim H, Tran J, Novokmet A, Malkin D.

Hum Mutat. 2016 Sep;37(9):889-92. doi: 10.1002/humu.23025. Epub 2016 Jun 27.

PubMed [citation]

PMID:: 27297285

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001469317.1

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

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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551585.1

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

Description

The TP53 p.Glu56= variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was also identified in dbSNP (ID: rs574255227) as "With Likely benign allele", ClinVar (classified as likely benign by Invitae, Ambry Genetics), Cosmic (1x found in Haematopoietic and lymphoid tissue), and in IARC TP53 Database (1x). The variant was not identified in COGR, or LOVD 3.0 databases. The variant was identified in control databases in 10 of 246224 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the South Asian population in 10 of 30780 chromosomes (freq: 0.0003), but not in the African, Other, Latino, European, Ashkenazi Jewish, East Asian, and Finnish populations. The p.Glu56= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The functional and co-segregation analysis of p.Glu56= transactivation in the germline, using a Dual-Luciferase Assay in TP53-null H1299, SAOS-2 and TP53 wild-type SK-N-AS cells, resulted in similar promoter activity levels to that of the WT TP53 plasmid. Authors concluded that it is likely that the p.Glu56= variant belongs to a class of rare single nucleotide polymorphisms (Said 2016). In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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

Last Updated: Nov 10, 2024

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