NM_000546.6(TP53):c.376T>A (p.Tyr126Asn) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 7, 2021
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:: RCV000801059.6

Allele description [Variation Report for NM_000546.6(TP53):c.376T>A (p.Tyr126Asn)]

NM_000546.6(TP53):c.376T>A (p.Tyr126Asn)

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.376T>A (p.Tyr126Asn)

HGVS:

NC_000017.11:g.7675236A>T
NG_017013.2:g.17315T>A
NM_000546.6:c.376T>AMANE SELECT
NM_001126112.3:c.376T>A
NM_001126113.3:c.376T>A
NM_001126114.3:c.376T>A
NM_001126115.2:c.-21T>A
NM_001126116.2:c.-21T>A
NM_001126117.2:c.-21T>A
NM_001126118.2:c.259T>A
NM_001276695.3:c.259T>A
NM_001276696.3:c.259T>A
NM_001276697.3:c.-102T>A
NM_001276698.3:c.-102T>A
NM_001276699.3:c.-102T>A
NM_001276760.3:c.259T>A
NM_001276761.3:c.259T>A
NP_000537.3:p.Tyr126Asn
NP_000537.3:p.Tyr126Asn
NP_001119584.1:p.Tyr126Asn
NP_001119585.1:p.Tyr126Asn
NP_001119586.1:p.Tyr126Asn
NP_001119590.1:p.Tyr87Asn
NP_001263624.1:p.Tyr87Asn
NP_001263625.1:p.Tyr87Asn
NP_001263689.1:p.Tyr87Asn
NP_001263690.1:p.Tyr87Asn
LRG_321t1:c.376T>A
LRG_321:g.17315T>A
LRG_321p1:p.Tyr126Asn
NC_000017.10:g.7578554A>T
NM_000546.4:c.376T>A
NM_000546.5:c.376T>A

Protein change:

Y126N

Links:

dbSNP: rs886039483

NCBI 1000 Genomes Browser:

rs886039483

Molecular consequence:

NM_001126115.2:c.-21T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-21T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-21T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-102T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-102T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-102T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.376T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.376T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.376T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.376T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.259T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.259T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.259T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.259T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.259T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Li-Fraumeni syndrome (LFS)
Synonyms:: Sarcoma family syndrome of Li and Fraumeni
Identifiers:: MONDO: MONDO:0018875; MedGen: C0085390; OMIM: PS151623

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thioredoxin domain-containing protein 12 precursor [Mus musculus]
thioredoxin domain-containing protein 12 precursor [Mus musculus]
gi|13384700|ref|NP_079610.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000940815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 7, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12826609, 29979965, 30224644, 30287823, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000940815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 7, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation.

Kotler E, Shani O, Goldfeld G, Lotan-Pompan M, Tarcic O, Gershoni A, Hopf TA, Marks DS, Oren M, Segal E.

Mol Cell. 2018 Jul 5;71(1):178-190.e8. doi: 10.1016/j.molcel.2018.06.012. Erratum in: Mol Cell. 2018 Sep 6;71(5):873. doi: 10.1016/j.molcel.2018.08.013.

PubMed [citation]

PMID:: 29979965

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000940815.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965, 30224644). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 428871). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 126 of the TP53 protein (p.Tyr126Asn).

#	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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