NM_000546.6(TP53):c.643A>T (p.Ser215Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 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:: RCV002361765.2

Allele description [Variation Report for NM_000546.6(TP53):c.643A>T (p.Ser215Cys)]

NM_000546.6(TP53):c.643A>T (p.Ser215Cys)

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.643A>T (p.Ser215Cys)

HGVS:

NC_000017.11:g.7674888T>A
NG_017013.2:g.17663A>T
NM_000546.6:c.643A>TMANE SELECT
NM_001126112.3:c.643A>T
NM_001126113.3:c.643A>T
NM_001126114.3:c.643A>T
NM_001126115.2:c.247A>T
NM_001126116.2:c.247A>T
NM_001126117.2:c.247A>T
NM_001126118.2:c.526A>T
NM_001276695.3:c.526A>T
NM_001276696.3:c.526A>T
NM_001276697.3:c.166A>T
NM_001276698.3:c.166A>T
NM_001276699.3:c.166A>T
NM_001276760.3:c.526A>T
NM_001276761.3:c.526A>T
NM_001407262.1:c.643A>T
NM_001407263.1:c.526A>T
NM_001407264.1:c.643A>T
NM_001407265.1:c.526A>T
NM_001407266.1:c.643A>T
NM_001407267.1:c.526A>T
NM_001407268.1:c.643A>T
NM_001407269.1:c.526A>T
NM_001407270.1:c.643A>T
NM_001407271.1:c.526A>T
NP_000537.3:p.Ser215Cys
NP_000537.3:p.Ser215Cys
NP_001119584.1:p.Ser215Cys
NP_001119584.1:p.Ser215Cys
NP_001119585.1:p.Ser215Cys
NP_001119585.1:p.Ser215Cys
NP_001119586.1:p.Ser215Cys
NP_001119586.1:p.Ser215Cys
NP_001119587.1:p.Ser83Cys
NP_001119587.1:p.Ser83Cys
NP_001119588.1:p.Ser83Cys
NP_001119588.1:p.Ser83Cys
NP_001119589.1:p.Ser83Cys
NP_001119589.1:p.Ser83Cys
NP_001119590.1:p.Ser176Cys
NP_001119590.1:p.Ser176Cys
NP_001263624.1:p.Ser176Cys
NP_001263625.1:p.Ser176Cys
NP_001263626.1:p.Ser56Cys
NP_001263627.1:p.Ser56Cys
NP_001263628.1:p.Ser56Cys
NP_001263689.1:p.Ser176Cys
NP_001263690.1:p.Ser176Cys
NP_001394191.1:p.Ser215Cys
NP_001394192.1:p.Ser176Cys
NP_001394193.1:p.Ser215Cys
NP_001394194.1:p.Ser176Cys
NP_001394195.1:p.Ser215Cys
NP_001394196.1:p.Ser176Cys
NP_001394197.1:p.Ser215Cys
NP_001394198.1:p.Ser176Cys
NP_001394199.1:p.Ser215Cys
NP_001394200.1:p.Ser176Cys
LRG_321t1:c.643A>T
LRG_321t2:c.643A>T
LRG_321t3:c.643A>T
LRG_321t4:c.643A>T
LRG_321t5:c.247A>T
LRG_321t6:c.247A>T
LRG_321t7:c.247A>T
LRG_321t8:c.526A>T
LRG_321:g.17663A>T
LRG_321:p.Ser215Cys
LRG_321p1:p.Ser215Cys
LRG_321p3:p.Ser215Cys
LRG_321p4:p.Ser215Cys
LRG_321p5:p.Ser83Cys
LRG_321p6:p.Ser83Cys
LRG_321p7:p.Ser83Cys
LRG_321p8:p.Ser176Cys
NC_000017.10:g.7578206T>A
NM_000546.4:c.643A>T
NM_000546.5:c.643A>T
NM_001126112.2:c.643A>T
NM_001126113.2:c.643A>T
NM_001126114.2:c.643A>T
NM_001126115.1:c.247A>T
NM_001126116.1:c.247A>T
NM_001126117.1:c.247A>T
NM_001126118.1:c.526A>T

Protein change:

S176C

Molecular consequence:

NM_000546.6:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126112.3:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126113.3:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126114.3:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126115.2:c.247A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126116.2:c.247A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126117.2:c.247A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001126118.2:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276695.3:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276696.3:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276697.3:c.166A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276698.3:c.166A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276699.3:c.166A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276760.3:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276761.3:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407262.1:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407263.1:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407264.1:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407265.1:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407266.1:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407267.1:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407268.1:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407269.1:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407270.1:c.643A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407271.1:c.526A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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LOC117406456 [Acipenser ruthenus]
LOC117406456 [Acipenser ruthenus]
Gene ID:117406456

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002660355	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 23, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10229196, 15781620 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002660355

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 23, 2021)

germline

clinical testing

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

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

Citations

PubMed

Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions.

Smith PD, Crossland S, Parker G, Osin P, Brooks L, Waller J, Philp E, Crompton MR, Gusterson BA, Allday MJ, Crook T.

Oncogene. 1999 Apr 15;18(15):2451-9.

PubMed [citation]

PMID:: 10229196

Lack of correlation between p53-dependent transcriptional activity and the ability to induce apoptosis among 179 mutant p53s.

Kakudo Y, Shibata H, Otsuka K, Kato S, Ishioka C.

Cancer Res. 2005 Mar 15;65(6):2108-14.

PubMed [citation]

PMID:: 15781620

Details of each submission

From Ambry Genetics, SCV002660355.2

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

Description

The p.S215C variant (also known as c.643A>T), located in coding exon 5 of the TP53 gene, results from an A to T substitution at nucleotide position 643. The serine at codon 215 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. This variant is in the DNA binding domain of the TP53 protein and is reported to have partially functional transactivation in yeast based assays (Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is proficient at growth suppression but has a dominant negative effect (Kotler E et al. Mol.Cell. 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). Additional studies showed equivocal results regarding the ability of this alteration to induce apoptosis (Kakudo Y et al. Cancer Res, 2005 Mar;65:2108-14; Smith PD et al. Oncogene, 1999 Apr;18:2451-9). 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 1, 2024

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