NM_000546.6(TP53):c.1101-1G>A AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000222547.7

Allele description

NM_000546.6(TP53):c.1101-1G>A

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.1101-1G>A

HGVS:

NC_000017.11:g.7669691C>T
NG_017013.2:g.22860G>A
NM_000546.6:c.1101-1G>AMANE SELECT
NM_001126112.3:c.1101-1G>A
NM_001126113.3:c.*120-1G>A
NM_001126114.3:c.*208-1G>A
NM_001126115.2:c.705-1G>A
NM_001126116.2:c.*208-1G>A
NM_001126117.2:c.*120-1G>A
NM_001126118.2:c.984-1G>A
NM_001276695.3:c.*120-1G>A
NM_001276696.3:c.*208-1G>A
NM_001276697.3:c.624-1G>A
NM_001276698.3:c.*208-1G>A
NM_001276699.3:c.*120-1G>A
NM_001276760.3:c.984-1G>A
NM_001276761.3:c.984-1G>A
NM_001407262.1:c.1101-1G>A
NM_001407263.1:c.984-1G>A
NM_001407264.1:c.1101-1G>A
NM_001407265.1:c.984-1G>A
NM_001407266.1:c.1101-1G>A
NM_001407267.1:c.984-1G>A
NM_001407268.1:c.*208-1G>A
NM_001407269.1:c.*208-1G>A
NM_001407270.1:c.*208-1G>A
NM_001407271.1:c.*208-1G>A
LRG_321t1:c.1101-1G>A
LRG_321t2:c.1101-1G>A
LRG_321:g.22860G>A
NC_000017.10:g.7573009C>T
NM_000546.4:c.1101-1G>A
NM_000546.5:c.1101-1G>A
NM_001126112.2:c.1101-1G>A

Links:

dbSNP: rs876658982

NCBI 1000 Genomes Browser:

rs876658982

Molecular consequence:

NM_000546.6:c.1101-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126112.3:c.1101-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126113.3:c.*120-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126114.3:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126115.2:c.705-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126116.2:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126117.2:c.*120-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001126118.2:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276695.3:c.*120-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276696.3:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276697.3:c.624-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276698.3:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276699.3:c.*120-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276760.3:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276761.3:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407262.1:c.1101-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407263.1:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407264.1:c.1101-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407265.1:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407266.1:c.1101-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407267.1:c.984-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407268.1:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407269.1:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407270.1:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001407271.1:c.*208-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000274903	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Jun 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20967502, 34452612 Citation Link,
SCV002582329	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000274903

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Jun 14, 2023)

germline

clinical testing

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

Citation Link,

SCV002582329

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 18, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor.

Pinto EM, Ribeiro RC, Kletter GB, Lawrence JP, Jenkins JJ, Wang J, Shurtleff S, McGregor L, Kriwacki RW, Zambetti GP.

Fam Cancer. 2011 Mar;10(1):141-6. doi: 10.1007/s10689-010-9392-z.

PubMed [citation]

PMID:: 20967502
PMCID:: PMC3036813

A first report of a rare TP53 variant associated with Li-Fraumeni syndrome manifesting as invasive breast cancer and malignant solitary fibrous tumor.

Prejac J, Dedić Plavetić N, Gotovac Jerčić K, Borovečki F.

World J Surg Oncol. 2021 Aug 27;19(1):254. doi: 10.1186/s12957-021-02370-8.

PubMed [citation]

PMID:: 34452612
PMCID:: PMC8399826

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000274903.8

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

Description

The c.1101-1G>A intronic variant results from a G to A one nucleotide upstream from coding exon 10 of the TP53 gene. This alteration was identified in an individual with a personal history of breast cancer and sarcoma (Prejac J et al. World J Surg Oncol, 2021 Aug;19:254). Another alteration at this same splice junction, c.1101-2A>G, was identified in a 2 year old patient with an adrenocortical tumor. RNA analysis from this tumor showed a deletion of the first 10 base pairs of exon 11 (coding exon 10) resulting in a frame shift and a predicted stop codon 82 nucleotides after the wild type termination codon (Pinto EM et al. Fam. Cancer 2011 Mar;10(1):141-6). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. Based on current evidence c.1101-1G>A is interpreted as a likely pathogenic moderate risk allele that may not be associated with classic LFS. Clinical correlation is advised.

#	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

From Genome-Nilou Lab, SCV002582329.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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