ClinVar Genomic variation as it relates to human health
NM_001128431.4(SLC39A14):c.751-9C>G
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_001128431.4(SLC39A14):c.751-9C>G
Variation ID: 446707 Accession: VCV000446707.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p21.3 8: 22415760 (GRCh38) [ NCBI UCSC ] 8: 22273273 (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 Dec 10, 2017 Oct 1, 2022 Nov 16, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001128431.4(SLC39A14):c.751-9C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001128431.4:c.751-9C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_015359.6:c.751-9C>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001135153.3:c.751-9C>G intron variant NM_001135154.3:c.751-9C>G intron variant NM_001351655.2:c.751-9C>G intron variant NM_001351656.2:c.751-9C>G intron variant NM_001351657.2:c.781-9C>G intron variant NM_001351658.2:c.781-9C>G intron variant NM_001351659.2:c.781-9C>G intron variant NM_001351660.2:c.751-9C>G intron variant NC_000008.11:g.22415760C>G NC_000008.10:g.22273273C>G NG_054890.1:g.53512C>G - Protein change
- Other names
- NP_056174.2:p.His251Profs*26
- IVS5AS, C-G, -9
- Canonical SPDI
- NC_000008.11:22415759:C:G
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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.
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- Comment on variant
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
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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
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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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SLC39A14 | - | - |
GRCh38 GRCh37 |
209 | 302 |
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
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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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Likely pathogenic (3) |
criteria provided, single submitter
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Nov 16, 2020 | RCV000515834.5 |
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
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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
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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
(Nov 16, 2020)
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criteria provided, single submitter
Method: curation
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Hypermanganesemia with dystonia 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001445944.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
The homozygous c.751-9C>G variant in SLC39A14 was identified by our study in 1 individual with hypermanganesemia with dystonia 2. This variant has also been reported … (more)
The homozygous c.751-9C>G variant in SLC39A14 was identified by our study in 1 individual with hypermanganesemia with dystonia 2. This variant has also been reported in the same individual as well as one other Emirati individual with hypermanganesemia with dystonia 2 (PMID: 29685658), but was absent from large population studies. This variant has been reported in ClinVar (Variation ID: 446707) and has been interpreted as pathogenic by GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK431123/). The presence of this variant in 2 affected homozygotes and in 2 individuals with hypermanganesemia with dystonia 2 increases the likelihood that the variant is pathogenic (PMID: 29685658). In vitro functional studies provide some evidence that the variant may slightly impact protein function (PMID: 29685658). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PM3, PP3, PS3_supporting (Richards 2015). (less)
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Pathogenic
(Apr 28, 2020)
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no assertion criteria provided
Method: literature only
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HYPERMANGANESEMIA WITH DYSTONIA 2
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001245268.1
First in ClinVar: May 04, 2020 Last updated: May 04, 2020 |
Comment on evidence:
In 2 unrelated children from the United Arab Emirates with hypermanganesemia with dystonia-2 (HMNDYT2; 617013), Rodan et al. (2018) identified a homozygous splice site mutation … (more)
In 2 unrelated children from the United Arab Emirates with hypermanganesemia with dystonia-2 (HMNDYT2; 617013), Rodan et al. (2018) identified a homozygous splice site mutation (c.751C-G, NM_001128431) in intron 5 (IVS5-9C-G) of the SLC39A14 gene, leading to aberrant splicing between exons 5 and 6 and an early stop codon in intron 5. The parents of 1 of the patients were confirmed to be heterozygous for the mutation. Quantitative RT-PCR analysis of SLC39A14 in fibroblasts from 1 patient confirmed aberrant splicing and showed decreased transcript levels around the region of the variant. (less)
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not provided
(-)
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no classification provided
Method: literature only
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Hypermanganesemia with dystonia 2
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000612145.2
First in ClinVar: Dec 10, 2017 Last updated: Oct 01, 2022 |
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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
HelpText-mined citations for rs1039778197 ...
HelpRecord last updated Mar 30, 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.
NCBI staff established an HGVS expression for this allele based on the trace in Figure 1b in the paper by Rodan et al., 2018 (PubMed 29685658).