ClinVar Genomic variation as it relates to human health
NM_014585.6(SLC40A1):c.610G>A (p.Gly204Ser)
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
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NM_014585.6(SLC40A1):c.610G>A (p.Gly204Ser)
Variation ID: 56158 Accession: VCV000056158.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q32.2 2: 189565504 (GRCh38) [ NCBI UCSC ] 2: 190430230 (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 Jul 24, 2013 Feb 14, 2024 Jul 23, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_014585.6:c.610G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055400.1:p.Gly204Ser missense NC_000002.12:g.189565504C>T NC_000002.11:g.190430230C>T NG_009027.1:g.20308G>A LRG_837:g.20308G>A LRG_837t1:c.610G>A LRG_837p1:p.Gly204Ser - Protein change
- G204S
- Other names
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- Canonical SPDI
- NC_000002.12:189565503: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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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SLC40A1 | - | - |
GRCh38 GRCh37 |
252 | 287 |
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
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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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not provided (1) |
no classification provided
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- | RCV000049568.1 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 23, 2022 | RCV000641707.10 |
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. |
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Likely pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hemochromatosis type 4
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894249.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Likely pathogenic
(Jul 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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Hemochromatosis type 4
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics and Genomics, Rennes University Hospital
Accession: SCV001445849.1
First in ClinVar: May 20, 2021 Last updated: May 20, 2021 |
Comment:
Identified in 15 patients harbouring clinical and biochemical symptomes of type 4 haemochromatosis
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Pathogenic
(Jul 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hemochromatosis type 4
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000763355.5
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant is present in population databases (rs387907377, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that … (more)
This variant is present in population databases (rs387907377, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SLC40A1 function (PMID: 23943237). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 56158). This missense change has been observed in individuals with hemochromatosis (PMID: 21199650, 31640930). It has also been observed to segregate with disease in related individuals. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 204 of the SLC40A1 protein (p.Gly204Ser). (less)
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Pathogenic
(Mar 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hemochromatosis type 4
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002318955.1
First in ClinVar: Apr 02, 2022 Last updated: Apr 02, 2022 |
Comment:
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 23943237) - PS3_moderate. The c.610G>A;p.(Gly204Ser) … (more)
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 23943237) - PS3_moderate. The c.610G>A;p.(Gly204Ser) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 56158; PMID: 23943237; PMID: 21199650; PMID: 21411349)-PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (FPN1) - PM1. The variant is present at low allele frequencies population databases (rs387907377 – gnomAD 0.00007955%; ABraOM 0.000427 frequency - http://abraom.ib.usp.br.) - PM2_supporting. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
germline
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Laboratoire de Génétique Moléculaire, CHU Pontchaillou
Accession: SCV000082626.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013 |
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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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Mutations and polymorphisms associated with iron overload in a series of 91 non-HFE haemochromatosis patients. | Borgel A | Clinics and research in hepatology and gastroenterology | 2020 | PMID: 31640930 |
Ferroportin diseases: functional studies, a link between genetic and clinical phenotype. | Détivaud L | Human mutation | 2013 | PMID: 23943237 |
Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients. | Santos PC | Blood cells, molecules & diseases | 2011 | PMID: 21411349 |
Sex and acquired cofactors determine phenotypes of ferroportin disease. | Le Lan C | Gastroenterology | 2011 | PMID: 21199650 |
Text-mined citations for rs387907377 ...
HelpRecord last updated Feb 14, 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.