VCV002443782.3 - ClinVar

NR_029422.2(RNU12):n.84C>T

Germline

Classification

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.

(1)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NR_029422.2(RNU12):n.84C>T

Variation ID: 2443782 Accession: VCV002443782.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 22q13.2 22: 42615327 (GRCh38) [ NCBI UCSC ] 22: 43011333 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Mar 18, 2023	Jun 9, 2024	Jul 6, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NR_029422.2:n.84C>T		non-coding transcript variant
NC_000022.11:g.42615327C>T
NC_000022.10:g.43011333C>T
NG_146004.1:g.693C>T

Protein change

Other names

43,011,333C-T

Canonical SPDI

NC_000022.11:42615326:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

OMIM: 620204.0001 VarSome

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
Gene	OMIM	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.
RNU12		-	-	GRCh38	6	17

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.
Spinocerebellar ataxia, autosomal recessive 33	Pathogenic (1)	no assertion criteria provided	Jul 6, 2023	RCV003152389.3

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.
Pathogenic (Jul 06, 2023)	no assertion criteria provided Method: literature only	SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 33 (1 family) Affected status: not provided Allele origin: germline	OMIM Accession: SCV003840980.3 First in ClinVar: Mar 18, 2023 Last updated: Jun 09, 2024	Publications: PubMed (1) PubMed: 27863452 Comment on evidence: In 6 affected members of a consanguineous kindred from Qatar with autosomal recessive spinocerebellar ataxia-33 (SCAR33; 620208), Elsaid et al. (2017) identified a homozygous C-to-T … (more) In 6 affected members of a consanguineous kindred from Qatar with autosomal recessive spinocerebellar ataxia-33 (SCAR33; 620208), Elsaid et al. (2017) identified a homozygous C-to-T transition at position 43,011,333 of chromosome 22 (chr22:43,011,333C-T), within the RNU12 gene. The mutation was also referred to as a C-to-T transition at nucleotide 84 of the RNU12 gene (84C-T). The mutation, which was found by a combination of whole-genome sequencing and homozygosity mapping and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the dbSNP, 1000 Genomes Project, or Exome Sequencing Project databases. The mutation affected a highly conserved area within the basepairing region at the base of the third stem-loop structure (SLIII) in this snRNA. RT-PCR of patient mononuclear blood cells showed increased levels of RNU12 in the patients, suggesting a transcriptional compensatory mechanism due to functionally defective U12 snRNA. Further studies of patient cells showed significant minor intron retention of U12-type genes, indicating splicing abnormalities. Transcriptome analysis showed differential expression of multiple RNA transcripts compared to controls, including several associated with cerebellar ataxia (e.g., ATXN10, 611150 and SLC9A6, 300231). (less)

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

Title	Author	Journal	Year	Link
Mutation in noncoding RNA RNU12 causes early onset cerebellar ataxia.	Elsaid MF	Annals of neurology	2017	PMID: 27863452

Text-mined citations for this variant ...

Record last updated Jun 10, 2024

ClinVar Genomic variation as it relates to human health

NR_029422.2(RNU12):n.84C>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...