NM_000546.6(TP53):c.672+1G>T AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 18, 2022
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:: RCV000776760.6

Allele description [Variation Report for NM_000546.6(TP53):c.672+1G>T]

NM_000546.6(TP53):c.672+1G>T

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.672+1G>T

HGVS:

NC_000017.11:g.7674858C>A
NG_017013.2:g.17693G>T
NM_000546.6:c.672+1G>TMANE SELECT
NM_001126112.3:c.672+1G>T
NM_001126113.3:c.672+1G>T
NM_001126114.3:c.672+1G>T
NM_001126115.2:c.276+1G>T
NM_001126116.2:c.276+1G>T
NM_001126117.2:c.276+1G>T
NM_001126118.2:c.555+1G>T
NM_001276695.3:c.555+1G>T
NM_001276696.3:c.555+1G>T
NM_001276697.3:c.195+1G>T
NM_001276698.3:c.195+1G>T
NM_001276699.3:c.195+1G>T
NM_001276760.3:c.555+1G>T
NM_001276761.3:c.555+1G>T
NM_001407262.1:c.672+1G>T
NM_001407263.1:c.555+1G>T
NM_001407264.1:c.672+1G>T
NM_001407265.1:c.555+1G>T
NM_001407266.1:c.672+1G>T
NM_001407267.1:c.555+1G>T
NM_001407268.1:c.672+1G>T
NM_001407269.1:c.555+1G>T
NM_001407270.1:c.672+1G>T
NM_001407271.1:c.555+1G>T
LRG_321t1:c.672+1G>T
LRG_321:g.17693G>T
NC_000017.10:g.7578176C>A
NM_000546.5:c.672+1G>T

Links:

dbSNP: rs863224499

NCBI 1000 Genomes Browser:

rs863224499

Molecular consequence:

NM_000546.6:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126112.3:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126113.3:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126114.3:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126115.2:c.276+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126116.2:c.276+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126117.2:c.276+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001126118.2:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276695.3:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276696.3:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276697.3:c.195+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276698.3:c.195+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276699.3:c.195+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276760.3:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001276761.3:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407262.1:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407263.1:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407264.1:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407265.1:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407266.1:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407267.1:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407268.1:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407269.1:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407270.1:c.672+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407271.1:c.555+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

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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RecName: Full=T-box transcription factor TBX10; Short=T-box protein 10
RecName: Full=T-box transcription factor TBX10; Short=T-box protein 10
gi|51338743|sp|O75333.2|TBX10_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000912404	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 11, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20805372, 25564201, 32658383, 34607348, 25741868
SCV002582371	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

SCV000912404

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 11, 2022)

germline

clinical testing

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

SCV002582371

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

A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations.

Wilson JR, Bateman AC, Hanson H, An Q, Evans G, Rahman N, Jones JL, Eccles DM.

J Med Genet. 2010 Nov;47(11):771-4. doi: 10.1136/jmg.2010.078113. Epub 2010 Aug 30. Erratum in: J Med Genet. 2011 Mar;48(3):216.

PubMed [citation]

PMID:: 20805372

The breast cancer immunophenotype of TP53-p.R337H carriers is different from that observed among other pathogenic TP53 mutation carriers.

Fitarelli-Kiehl M, Giacomazzi J, Santos-Silva P, Graudenz MS, Palmero EI, Michelli RA, Achatz MI, de Toledo Osório CA, de Faria Ferraz VE, Picanço CG, Ashton-Prolla P.

Fam Cancer. 2015 Jun;14(2):333-6. doi: 10.1007/s10689-015-9779-y.

PubMed [citation]

PMID:: 25564201

See all PubMed Citations (5)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000912404.3

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

Description

This variant causes a G to T nucleotide substitution at the +1 position of intron 6 of the TP53 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has been reported in individuals affected with rhabdomyosarcoma meeting Chompret criteria (PMID: 32658383), breast cancer (PMID: 20805372, 25564201), and hairy cell leukemia variant (PMID 34607348). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of TP53 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.

#	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, SCV002582371.1

#	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: Jul 15, 2024

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