ClinVar Genomic variation as it relates to human health
NM_000546.6(TP53):c.108G>A (p.Pro36=)
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.108G>A (p.Pro36=)
Variation ID: 132708 Accession: VCV000132708.64
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17p13.1 17: 7676261 (GRCh38) [ NCBI UCSC ] 17: 7579579 (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 Mar 24, 2015 May 1, 2024 Feb 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000546.6:c.108G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000537.3:p.Pro36= synonymous NM_001126112.3:c.108G>A NP_001119584.1:p.Pro36= synonymous NM_001126113.3:c.108G>A NP_001119585.1:p.Pro36= synonymous NM_001126114.3:c.108G>A NP_001119586.1:p.Pro36= synonymous NM_001126118.2:c.-10G>A 5 prime UTR NM_001276695.3:c.-10G>A 5 prime UTR NM_001276696.3:c.-10G>A 5 prime UTR NM_001276760.3:c.-10G>A 5 prime UTR NM_001276761.3:c.-10G>A 5 prime UTR NC_000017.11:g.7676261C>T NC_000017.10:g.7579579C>T NG_017013.2:g.16290G>A LRG_321:g.16290G>A LRG_321t1:c.108G>A LRG_321p1:p.Pro36= LRG_321t3:c.108G>A LRG_321p3:p.Pro36= - Protein change
- Other names
- NP_000537.3:p.Pro36=
- Canonical SPDI
- NC_000017.11:7676260:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00759 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00759
1000 Genomes Project 30x 0.00781
The Genome Aggregation Database (gnomAD) 0.00974
Trans-Omics for Precision Medicine (TOPMed) 0.01110
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01130
Exome Aggregation Consortium (ExAC) 0.01261
The Genome Aggregation Database (gnomAD), exomes 0.01328
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 |
3307 | 3402 |
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. |
---|---|---|---|---|
Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV000119149.17 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jun 18, 2022 | RCV000162410.8 | |
Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000244898.27 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001358051.4 | |
Benign (2) |
criteria provided, single submitter
|
Mar 3, 2015 | RCV001573454.7 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 19, 2022 | RCV002225349.6 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jul 7, 2023 | RCV000611879.10 |
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. |
|
---|---|---|---|---|---|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305113.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
Benign
(Jul 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000884713.2
First in ClinVar: Feb 18, 2019 Last updated: Feb 10, 2020 |
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000407072.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002505080.1
First in ClinVar: Apr 29, 2022 Last updated: Apr 29, 2022 |
Number of individuals with the variant: 39
Geographic origin: South Africa
|
|
Benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515175.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
|
Benign
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002582429.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Benign
(Jun 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002583091.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
|
|
Benign
(Mar 31, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537364.1
First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015 |
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001846757.1
First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021 |
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015625.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551103.4
First in ClinVar: Jul 23, 2022 Last updated: Aug 18, 2023 |
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Li-Fraumeni syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000153868.10
First in ClinVar: Jun 03, 2014 Last updated: Feb 28, 2024 |
|
|
Benign
(Dec 17, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000212746.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000692097.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Li-Fraumeni syndrome 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733711.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799362.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Likely benign
(Feb 20, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000788223.1
First in ClinVar: Mar 24, 2015 Last updated: Mar 24, 2015 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553694.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The TP53 p.Pro36= variant was identified in 4 of 152 proband chromosomes (frequency: 0.03) from French Canadian and Brazilian individuals or families with hereditary breast … (more)
The TP53 p.Pro36= variant was identified in 4 of 152 proband chromosomes (frequency: 0.03) from French Canadian and Brazilian individuals or families with hereditary breast and ovarian cancers or Li-Fraumeni like syndrome (Arcand 2015, Palmero 2016). The variant was also identified in 3 of 28 gastric tumours, either individually or in combination with the TP53 P72R polymorphism (Juvan 2007); and in 1 of 101 sporadic CRC tumours (Lopez 2012). The variant was identified in ClinVar (classified benign by Invitae, Ambry Genetics, Prevention Genetics and Color Genomics Inc., and likely benign by Illumina), Clinvitae (classifications benign and conflicting interpretations of pathogenicity) and the IARC TP53 Database (as a validated polymorphism). The variant was not identified in Genesight-COGR, Cosmic, LOVD 3.0, UMD TP52 Mutation Database (not available), and Database of germline p53 mutations. The variant was identified in control databases in 3520 (38 homozygous) of 277012 chromosomes at a frequency of 0.013 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: Latino in 1043 of 34398 chromosomes (freq: 0.03), European (Non-Finnish) in 1769 of 126630 chromosomes (freq: 0.014), Other in 77 of 6456 chromosomes (freq: 0.012), and South Asian in 331 of 30778 chromosomes (freq: 0.011). The p.Pro36Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808706.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906196.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954402.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974732.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
Text-mined citations for rs1800370 ...
HelpRecord last updated May 01, 2024
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.