NM_000546.6(TP53):c.379T>A (p.Ser127Thr) AND Li-Fraumeni syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 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:: RCV001038263.9

Allele description [Variation Report for NM_000546.6(TP53):c.379T>A (p.Ser127Thr)]

NM_000546.6(TP53):c.379T>A (p.Ser127Thr)

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.379T>A (p.Ser127Thr)

HGVS:

NC_000017.11:g.7675233A>T
NG_017013.2:g.17318T>A
NM_000546.6:c.379T>AMANE SELECT
NM_001126112.3:c.379T>A
NM_001126113.3:c.379T>A
NM_001126114.3:c.379T>A
NM_001126115.2:c.-18T>A
NM_001126116.2:c.-18T>A
NM_001126117.2:c.-18T>A
NM_001126118.2:c.262T>A
NM_001276695.3:c.262T>A
NM_001276696.3:c.262T>A
NM_001276697.3:c.-99T>A
NM_001276698.3:c.-99T>A
NM_001276699.3:c.-99T>A
NM_001276760.3:c.262T>A
NM_001276761.3:c.262T>A
NP_000537.3:p.Ser127Thr
NP_001119584.1:p.Ser127Thr
NP_001119585.1:p.Ser127Thr
NP_001119586.1:p.Ser127Thr
NP_001119590.1:p.Ser88Thr
NP_001263624.1:p.Ser88Thr
NP_001263625.1:p.Ser88Thr
NP_001263689.1:p.Ser88Thr
NP_001263690.1:p.Ser88Thr
LRG_321t1:c.379T>A
LRG_321:g.17318T>A
NC_000017.10:g.7578551A>T
NM_000546.4:c.379T>A
NM_000546.5:c.379T>A

Protein change:

S127T

Links:

dbSNP: rs1597371694

NCBI 1000 Genomes Browser:

rs1597371694

Molecular consequence:

NM_001126115.2:c.-18T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-18T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-18T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-99T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-99T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-99T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.379T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.379T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.379T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.379T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.262T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.262T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.262T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.262T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.262T>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001201727	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 12826609, 30224644, 29979965, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001201727

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2021)

germline

clinical testing

PubMed (4)
[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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001201727.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces serine with threonine at codon 127 of the TP53 protein (p.Ser127Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related conditions. ClinVar contains an entry for this variant (Variation ID: 824232). Experimental studies have shown that this variant affects TP53 protein function (PMID: 12826609, 30224644, 29979965). 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.

#	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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