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NM_000546.6(TP53):c.919+1G>A

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Interpretation:
Likely pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
4 (Most recent: Aug 20, 2021)
Last evaluated:
Aug 28, 2019
Accession:
VCV000633606.5
Variation ID:
633606
Description:
single nucleotide variant
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NM_000546.6(TP53):c.919+1G>A

Allele ID
622038
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7673700 (GRCh38) GRCh38 UCSC
17: 7577018 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_321t7:c.523+1G>A
NC_000017.10:g.7577018C>T
NC_000017.11:g.7673700C>T
... more HGVS
Protein change
-
Other names
NM_001276761.1:c.802+1G>A
Canonical SPDI
NC_000017.11:7673699:C:T
Functional consequence
sequence_variant_affecting_splicing [Sequence Ontology SO:1000071]
Intron inclusion between exons 8 & 9, based on review of RNA-seq in TCGA-V5-A7RC-01B tumor which has TP53 NM_000546.6:c.919+1G>A variant [submitted by MutSpliceDB: a database of splice sites variants effects on splicing,NIH]
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
dbSNP: rs1131691039
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 reviewed by expert panel Aug 28, 2019 RCV000991150.3
Pathogenic 1 no assertion criteria provided May 21, 2019 RCV000782136.1
not provided 1 no assertion provided - RCV001578272.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
TP53 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
2202 2265

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Aug 28, 2019)
reviewed by expert panel
Method: curation
Li-Fraumeni syndrome
(Autosomal dominant inheritance)
Allele origin: germline
ClinGen TP53 Variant Curation Expert Panel,ClinGen
FDA Recognized Database
Accession: SCV001142564.1
Submitted: (Sep 23, 2019)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
The c.919+1G>A is canonical splice variant predicted to result in a truncated or absent protein (PVS1_Strong). This variant is absent in the gnomAD cohort (PM2_Supporting; … (more)
Pathogenic
(Oct 09, 2020)
criteria provided, single submitter
Method: clinical testing
Li-Fraumeni syndrome
Allele origin: germline
Invitae
Accession: SCV001382474.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change affects a donor splice site in intron 8 of the TP53 gene. It is expected to disrupt RNA splicing and likely results … (more)
Pathogenic
(May 21, 2019)
no assertion criteria provided
Method: clinical testing
Li-Fraumeni syndrome 1
(Autosomal dominant inheritance)
Allele origin: germline
Academic Center for Education, Culture and Research, Motamed Cancer Institute
Accession: SCV000914200.1
Submitted: (May 26, 2019)
Evidence details
not provided
(-)
no assertion provided
Method: in vivo
not provided
Allele origin: somatic
MutSpliceDB: a database of splice sites variants effects on splicing,NIH
Accession: SCV001805840.1
Submitted: (Aug 20, 2021)
Evidence details

Functional evidence

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Functional consequence Method Result Submitter Supporting information
sequence_variant_affecting_splicing
  1. Based on review of RNA-seq data in sample with variant.
  1. Intron inclusion between exons 8 & 9
MutSpliceDB: a database of splice sites variants effects on splicing,NIH
Accession: SCV001805840.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Intron inclusion between exons 8 & 9, based on review of RNA-seq in TCGA-V5-A7RC-01B tumor which has TP53 NM_000546.6:c.919+1G>A variant

Citations for this variant

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Title Author Journal Year Link
Clinical characteristics and registry-validated extended pedigrees of germline TP53 mutation carriers in Denmark. Stoltze U PloS one 2018 PMID: 29324801
Contribution of de novo and mosaic <i>TP53</i> mutations to Li-Fraumeni syndrome. Renaux-Petel M Journal of medical genetics 2018 PMID: 29070607
A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations. Wilson JR Journal of medical genetics 2010 PMID: 20805372
TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. Ruijs MW Journal of medical genetics 2010 PMID: 20522432
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
https://brb.nci.nih.gov/cgi-bin/splicing/splicing_evidence.cgi?caid=CA397836247 - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/e5597807-7124-425a-b33a-5c6af85c5edc - - - -

Text-mined citations for rs1131691039...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021