ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.920-1G>T
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000546.6(TP53):c.920-1G>T
Variation ID: 480765 Accession: VCV000480765.9
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7673609 (GRCh38) [ NCBI UCSC ] 17: 7576927 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 1, 2018 Nov 29, 2022 Jun 18, 2022 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- Other names
- NM_000546.6:c.920-1G>T
- Canonical SPDI
- NC_000017.11:7673608:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- sequence_variant_affecting_splicing Sequence Ontology [SO:1000071]
- Intron inclusion between exons 8 & 9, based on review of RNA-seq in TCGA-KK-A7AU-01A tumor which has TP53 NM_000546.6:c.920-1G>T variant [submitted by MutSpliceDB: a database of splice sites variants effects on splicing, NIH]
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
TP53 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3196 | 3291 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2022 | RCV000563356.4 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000785455.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jul 26, 2021 | RCV001553698.2 | |
not provided (1) |
no classification provided
|
- | RCV001672879.2 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jun 18, 2022 | RCV002289799.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Jul 26, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001774660.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Variant summary: TP53 c.920-1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: TP53 c.920-1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: 4/4 predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251470 control chromosomes (gnomAD). c.920-1G>T has been reported in the literature in multiple families/individuals affected with tumors belonging to the Li-Fraumeni Syndrome tumor spectrum (e.g. Gonzalez_2009, Wu_2011, Rana_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002582443.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Pathogenic
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002583105.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Pathogenic
(Jun 06, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000664442.4
First in ClinVar: Jan 01, 2018 Last updated: Nov 29, 2022 |
Comment:
The c.920-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 8 of the TP53 gene. This altetation, … (more)
The c.920-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 8 of the TP53 gene. This altetation, designated as IVS8-1G>T, has been reported in a family that met Chompret criteria (Gonzalez KD et al. J. Med. Genet., 2009 Oct;46:689-93). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. (less)
Number of individuals with the variant: 1
|
|
Likely pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Neoplasm of ovary
Affected status: yes
Allele origin:
somatic
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000924027.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
not provided
(-)
|
no classification provided
Method: research
|
not provided
Affected status: not applicable
Allele origin:
somatic
|
MutSpliceDB: a database of splice sites variants effects on splicing, NIH
Accession: SCV001890922.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment on evidence:
Intron inclusion between exons 8 & 9, based on review of RNA-seq in TCGA-KK-A7AU-01A tumor which has TP53 NM_000546.6:c.920-1G>T variant
Method: Based on review of RNA-seq data in sample with variant.
Result:
Intron inclusion between exons 8 & 9
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
sequence_variant_affecting_splicing
|
|
|
MutSpliceDB: a database of splice sites variants effects on splicing, NIH
Accession: SCV001890922.1
|
Comment:
Intron inclusion between exons 8 & 9, based on review of RNA-seq in TCGA-KK-A7AU-01A tumor which has TP53 NM_000546.6:c.920-1G>T variant
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Genotype-phenotype associations among panel-based TP53+ subjects. | Rana HQ | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 31105275 |
The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. | McNamara CJ | Blood advances | 2018 | PMID: 30327374 |
Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | Döhner H | Blood | 2017 | PMID: 27895058 |
The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. | Stengel A | Leukemia | 2017 | PMID: 27680515 |
TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. | Welch JS | The New England journal of medicine | 2016 | PMID: 27959731 |
TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. | Kadia TM | Cancer | 2016 | PMID: 27463065 |
Genomic Classification and Prognosis in Acute Myeloid Leukemia. | Papaemmanuil E | The New England journal of medicine | 2016 | PMID: 27276561 |
Specific TP53 Mutants Overrepresented in Ovarian Cancer Impact CNV, TP53 Activity, Responses to Nutlin-3a, and Cell Survival. | Mullany LK | Neoplasia (New York, N.Y.) | 2015 | PMID: 26585234 |
TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. | Hou HA | Blood cancer journal | 2015 | PMID: 26230955 |
TP53 mutation characteristics in therapy-related myelodysplastic syndromes and acute myeloid leukemia is similar to de novo diseases. | Ok CY | Journal of hematology & oncology | 2015 | PMID: 25952993 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Functional characterisation of p53 mutants identified in breast cancers with suboptimal responses to anthracyclines or mitomycin. | Berge EO | Biochimica et biophysica acta | 2013 | PMID: 23246812 |
A novel hierarchical prognostic model of AML solely based on molecular mutations. | Grossmann V | Blood | 2012 | PMID: 22915647 |
TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. | Rücker FG | Blood | 2012 | PMID: 22186996 |
TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. | Jädersten M | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2011 | PMID: 21519010 |
Dominant-negative features of mutant TP53 in germline carriers have limited impact on cancer outcomes. | Monti P | Molecular cancer research : MCR | 2011 | PMID: 21343334 |
Joint effects of germ-line TP53 mutation, MDM2 SNP309, and gender on cancer risk in family studies of Li-Fraumeni syndrome. | Wu CC | Human genetics | 2011 | PMID: 21305319 |
Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation. | Jordan JJ | Molecular cancer research : MCR | 2010 | PMID: 20407015 |
High frequency of de novo mutations in Li-Fraumeni syndrome. | Gonzalez KD | Journal of medical genetics | 2009 | PMID: 19556618 |
Transcriptional functionality of germ line p53 mutants influences cancer phenotype. | Monti P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2007 | PMID: 17606709 |
Functional analysis and molecular modeling show a preserved wild-type activity of p53(C238Y). | Ferrone M | Molecular cancer therapeutics | 2006 | PMID: 16818505 |
A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants. | Friedler A | Proceedings of the National Academy of Sciences of the United States of America | 2002 | PMID: 11782540 |
https://brb.nci.nih.gov/cgi-bin/splicing/splicing_evidence.cgi?caid=CA397836174 | - | - | - | - |
click to load more click to collapse |
Text-mined citations for rs587781702 ...
HelpRecord last updated Dec 25, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.