ClinVar Genomic variation as it relates to human health
NM_183065.4(TMEM107):c.*686A>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_183065.4(TMEM107):c.*686A>G
Variation ID: 929280 Accession: VCV000929280.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17p13.1 17: 8173517 (GRCh38) [ NCBI UCSC ] 17: 8076835 (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 Jun 27, 2020 May 12, 2024 Jan 23, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_183065.4:c.*686A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
3 prime UTR NM_001351278.2:c.*686A>G 3 prime UTR NM_001351279.2:c.*686A>G 3 prime UTR NM_001351280.2:c.*686A>G 3 prime UTR NM_032354.5:c.*686A>G 3 prime UTR NR_033294.2:n.72A>G non-coding transcript variant NR_147092.2:n.937A>G non-coding transcript variant NC_000017.11:g.8173517T>C NC_000017.10:g.8076835T>C NG_054916.1:g.7895A>G NG_056674.1:g.5072A>G LRG_1204:g.5072A>G LRG_1204t1:n.72A>G - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:8173516:T:C
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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.
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
- Links
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
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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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SNORD118 | - | - | GRCh38 | - | 196 | |
TMEM107 | - | - |
GRCh38 GRCh37 |
19 | 312 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 23, 2024 | RCV001194492.4 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 11, 2023 | RCV001815472.18 |
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
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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
(Jun 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Leukoencephalopathy with calcifications and cysts
Affected status: unknown
Allele origin:
unknown
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Illumina Laboratory Services, Illumina
Accession: SCV004101312.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
Comment:
The SNORD118 g.8076835T>C variant, also referred to as NR_033294.1 n.72A>G, is a non-protein coding variant that has been reported in trans with a second SNORD118 … (more)
The SNORD118 g.8076835T>C variant, also referred to as NR_033294.1 n.72A>G, is a non-protein coding variant that has been reported in trans with a second SNORD118 variant in ten unrelated individuals with a phenotype consistent with leukoencephalopathy with calcifications and cysts (PMID: 27571260; 28177126; 30794980; 31521395; 33029936). It also co-segregated with the phenotype in an affected sibling in one family. This variant is not observed at a significant frequency in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. This variant is located near the LSm binding site within a hotspot in the transcribed portion of the U8 snoRNA (PMID: 33029936). Based on the available evidence, the SNORD118 g.8076835T>C variant is classified as likely pathogenic for leukoencephalopathy with calcifications and cysts. (less)
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Pathogenic
(Dec 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002231299.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This variant occurs in the SNORD118 gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in … (more)
This variant occurs in the SNORD118 gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (rs201558321, gnomAD 0.02%). This variant has been observed in individuals with cerebral microangiopathy leukoencephalopathy with calcifications and cysts (PMID: 27571260, 28177126, 33029936). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 929280). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Leukoencephalopathy with calcifications and cysts
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004803731.1
First in ClinVar: Mar 30, 2024 Last updated: Mar 30, 2024 |
Comment:
Variant summary: SNORD118 n.72A>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 232094 control chromosomes … (more)
Variant summary: SNORD118 n.72A>G alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 6.9e-05 in 232094 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. n.72A>G has been reported in the literature in compound heterozygous individuals affected with Leukoencephalopathy With Calcifications And Cysts (e.g., Jenkinson_2016, Iwama_2017, Shtaya_2019, Crow_2021, Osman_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33029936, 28177126, 27571260, 30794980, 31521395). ClinVar contains an entry for this variant (Variation ID: 929280). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Mar 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002063569.15
First in ClinVar: Jan 29, 2022 Last updated: May 12, 2024 |
Number of individuals with the variant: 3
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Pathogenic
(Apr 06, 2020)
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no assertion criteria provided
Method: clinical testing
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Leukoencephalopathy, brain calcifications, and cysts
Affected status: yes
Allele origin:
germline
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Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine
Accession: SCV001364117.1
First in ClinVar: Jun 27, 2020 Last updated: Jun 27, 2020 |
Number of individuals with the variant: 4
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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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Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum. | Crow YJ | American journal of medical genetics. Part A | 2021 | PMID: 33029936 |
Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review. | Osman O | Revue neurologique | 2020 | PMID: 31521395 |
Leukoencephalopathy, Intracranial Calcifications, Cysts, and SNORD118 Mutation (Labrune Syndrome) with Obstructive Hydrocephalus. | Shtaya A | World neurosurgery | 2019 | PMID: 30794980 |
Identification of novel SNORD118 mutations in seven patients with leukoencephalopathy with brain calcifications and cysts. | Iwama K | Clinical genetics | 2017 | PMID: 28177126 |
Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. | Jenkinson EM | Nature genetics | 2016 | PMID: 27571260 |
Text-mined citations for rs201558321 ...
HelpRecord last updated May 12, 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.