NM_000546.6(TP53):c.380C>A (p.Ser127Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 2, 2018
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:: RCV002352420.3

Allele description [Variation Report for NM_000546.6(TP53):c.380C>A (p.Ser127Tyr)]

NM_000546.6(TP53):c.380C>A (p.Ser127Tyr)

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.380C>A (p.Ser127Tyr)

HGVS:

NC_000017.11:g.7675232G>T
NG_017013.2:g.17319C>A
NM_000546.6:c.380C>AMANE SELECT
NM_001126112.3:c.380C>A
NM_001126113.3:c.380C>A
NM_001126114.3:c.380C>A
NM_001126115.2:c.-17C>A
NM_001126116.2:c.-17C>A
NM_001126117.2:c.-17C>A
NM_001126118.2:c.263C>A
NM_001276695.3:c.263C>A
NM_001276696.3:c.263C>A
NM_001276697.3:c.-98C>A
NM_001276698.3:c.-98C>A
NM_001276699.3:c.-98C>A
NM_001276760.3:c.263C>A
NM_001276761.3:c.263C>A
NP_000537.3:p.Ser127Tyr
NP_000537.3:p.Ser127Tyr
NP_001119584.1:p.Ser127Tyr
NP_001119585.1:p.Ser127Tyr
NP_001119586.1:p.Ser127Tyr
NP_001119590.1:p.Ser88Tyr
NP_001263624.1:p.Ser88Tyr
NP_001263625.1:p.Ser88Tyr
NP_001263689.1:p.Ser88Tyr
NP_001263690.1:p.Ser88Tyr
LRG_321t1:c.380C>A
LRG_321t2:c.380C>A
LRG_321:g.17319C>A
LRG_321p1:p.Ser127Tyr
NC_000017.10:g.7578550G>T
NM_000546.4:c.380C>A
NM_000546.5:c.380C>A
NM_001126112.2(TP53):c.380C>A
p.Ser127Tyr
NC_000017.11:g.7675232G>T

Protein change:

S127Y

Links:

dbSNP: rs730881999

NCBI 1000 Genomes Browser:

rs730881999

Molecular consequence:

NM_001126115.2:c.-17C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126116.2:c.-17C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001126117.2:c.-17C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276697.3:c.-98C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276698.3:c.-98C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001276699.3:c.-98C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000546.6:c.380C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.380C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.380C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.380C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.263C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Hereditary neoplastic syndrome; 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
SCV002622815	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 2, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002622815

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 2, 2018)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV002622815.2

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

Description

The p.S127Y variant (also known as c.380C>A), located in coding exon 4 of the TP53 gene, results from a C to A substitution at nucleotide position 380. The serine at codon 127 is replaced by tyrosine, an amino acid with dissimilar properties. This alteration has been reported as a somatic mutation 12 times in various tumors, but not as a germline mutation by the IARC TP53 database (Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum. Mutat. 2007 Jun;28:622-9). This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity (IARC TP53 database; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 16, 2025

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