ClinVar Genomic variation as it relates to human health
NM_032444.4(SLX4):c.2359G>A (p.Glu787Lys)
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.
Uncertain significance(5); Benign(1); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032444.4(SLX4):c.2359G>A (p.Glu787Lys)
Variation ID: 407938 Accession: VCV000407938.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.3 16: 3591279 (GRCh38) [ NCBI UCSC ] 16: 3641280 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Aug 28, 2017 Apr 15, 2024 Jan 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032444.4:c.2359G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115820.2:p.Glu787Lys missense NC_000016.10:g.3591279C>T NC_000016.9:g.3641280C>T NG_028123.1:g.25306G>A LRG_503:g.25306G>A LRG_503t1:c.2359G>A - Protein change
- E787K
- Other names
- -
- Canonical SPDI
- NC_000016.10:3591278:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00115
Exome Aggregation Consortium (ExAC) 0.00122
The Genome Aggregation Database (gnomAD) 0.00125
The Genome Aggregation Database (gnomAD), exomes 0.00126
Trans-Omics for Precision Medicine (TOPMed) 0.00141
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 | ||
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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. |
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SLX4 | - | - |
GRCh38 GRCh37 |
2148 | 2209 |
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. |
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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Dec 1, 2023 | RCV000464063.26 | |
Uncertain significance (2) |
criteria provided, single submitter
|
Nov 29, 2016 | RCV000502866.8 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 22, 2024 | RCV001081719.9 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Nov 23, 2020 | RCV001121832.9 | |
Likely benign (1) |
criteria provided, single submitter
|
Jan 27, 2020 | RCV003912802.1 |
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. |
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Uncertain significance
(Nov 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000597139.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group P
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001280485.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Nov 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group P
Affected status: yes
Allele origin:
unknown
|
Baylor Genetics
Study: CSER-TexasKidsCanSeq
Accession: SCV001482655.1 First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely benign
(Feb 13, 2021)
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criteria provided, single submitter
Method: curation
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002529300.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Uncertain significance
(Oct 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002586578.2
First in ClinVar: Oct 29, 2022 Last updated: Mar 04, 2023 |
Comment:
Observed in individuals with breast or ovarian cancer, but also in unaffected controls (de Garibay 2013, Bakker 2013, Shah 2013, Song 2020); Published functional studies … (more)
Observed in individuals with breast or ovarian cancer, but also in unaffected controls (de Garibay 2013, Bakker 2013, Shah 2013, Song 2020); Published functional studies demonstrate cell growth similar to wild-type following exposure to Mitomycin C (Bakker 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23211700, 22911665, 23840564, 28678401, 32546565, 34426522) (less)
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Uncertain significance
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010279.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Benign
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000547481.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Likely benign
(Jan 27, 2020)
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criteria provided, single submitter
Method: clinical testing
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SLX4-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004730813.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001150768.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
SLX4: BP4
Number of individuals with the variant: 4
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Likely benign
(Aug 31, 2012)
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no assertion criteria provided
Method: curation
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not specified
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001364629.1
First in ClinVar: Jun 27, 2020 Last updated: Jun 27, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker.
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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 |
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Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer. | Song H | Journal of medical genetics | 2021 | PMID: 32546565 |
Assessment of SLX4 Mutations in Hereditary Breast Cancers. | Shah S | PloS one | 2013 | PMID: 23840564 |
Low prevalence of SLX4 loss-of-function mutations in non-BRCA1/2 breast and/or ovarian cancer families. | de Garibay GR | European journal of human genetics : EJHG | 2013 | PMID: 23211700 |
Analysis of the novel fanconi anemia gene SLX4/FANCP in familial breast cancer cases. | Bakker JL | Human mutation | 2013 | PMID: 22911665 |
Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases. | Catucci I | PloS one | 2012 | PMID: 22383991 |
Text-mined citations for rs140600202 ...
HelpRecord last updated Apr 15, 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.