ClinVar Miner

Submissions for variant NM_001128431.4(SLC39A14):c.751-9C>G

dbSNP: rs1039778197
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000515834 SCV001445944 likely pathogenic Hypermanganesemia with dystonia 2 2020-11-16 criteria provided, single submitter curation 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).
GeneReviews RCV000515834 SCV000612145 not provided Hypermanganesemia with dystonia 2 no assertion provided literature only
OMIM RCV000515834 SCV001245268 pathogenic Hypermanganesemia with dystonia 2 2020-04-28 no assertion criteria provided literature only

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