VCV000265788.31 - ClinVar

NM_183065.4(TMEM107):c.*759C>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.

(7)

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/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_183065.4(TMEM107):c.*759C>T

Variation ID: 265788 Accession: VCV000265788.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17p13.1 17: 8173444 (GRCh38) [ NCBI UCSC ] 17: 8076762 (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	Oct 14, 2016	Oct 20, 2024	Apr 3, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_183065.4:c.*759C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_001351278.2:c.*759C>T		3 prime UTR
NM_001351279.2:c.*759C>T		3 prime UTR
NM_001351280.2:c.*759C>T		3 prime UTR
NM_032354.5:c.*759C>T		3 prime UTR
NR_147092.2:n.1010C>T		non-coding transcript variant
NC_000017.11:g.8173444G>A
NC_000017.10:g.8076762G>A
NG_054916.1:g.7968C>T
NG_056674.1:g.5145C>T
LRG_1204:g.5145C>T

... more HGVS ... less HGVS

Protein change

Other names

TER9C-T

Canonical SPDI

NC_000017.11:8173443:G:A

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.

0.00080 (A)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00174

Trans-Omics for Precision Medicine (TOPMed) 0.00210

1000 Genomes Project 30x 0.00062

1000 Genomes Project 0.00080

The Genome Aggregation Database (gnomAD) 0.00162

Links

ClinGen: CA8370542 OMIM: 616663.0006 dbSNP: rs201787275 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.
SNORD118		-	-	GRCh38	-	197
TMEM107		-	-	GRCh38 GRCh37	21	323

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.
Leukoencephalopathy with calcifications and cysts	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Jan 3, 2024	RCV000256201.5
not provided	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Apr 3, 2024	RCV000762201.25

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 (Aug 25, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Leukoencephalopathy with calcifications and cysts Affected status: yes Allele origin: maternal	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology Study: HudsonAlpha-AGHI-WGS Accession: SCV004035173.1 First in ClinVar: Sep 23, 2023 Last updated: Sep 23, 2023	Number of individuals with the variant: 1 Clinical Features: Facial palsy (present) , CNS hypermyelination (present) , Falls (present) , Leukodystrophy (present) , Obesity (present) , Tremor (present) , Gait disturbance (present) , Dysarthria … (more) Facial palsy (present) , CNS hypermyelination (present) , Falls (present) , Leukodystrophy (present) , Obesity (present) , Tremor (present) , Gait disturbance (present) , Dysarthria (present) , Spasticity (present) , Cerebellar ataxia (present) (less)
Pathogenic (Jan 03, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Leukoencephalopathy with calcifications and cysts (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen Accession: SCV004222610.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Clinical Features: Basal ganglia calcification (present)
Pathogenic (Jun 15, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV004238380.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024
Likely pathogenic (Apr 03, 2024)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005371735.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Comment: Functional studies provide conflicting evidence, with one study suggesting this variant alters processing of the precursor U8 snoRNAs while another study suggests this variant is … (more) Functional studies provide conflicting evidence, with one study suggesting this variant alters processing of the precursor U8 snoRNAs while another study suggests this variant is functional (PMID: 27571260, 32359472); Variant in a snoRNA that alters a C:G Watson-Crick base pair to a U:G wobble base pair in the 3' extension (PMID: 32359472); This variant is associated with the following publications: (PMID: 32359472, 33029936, 27571260, 34426522, 37761957, 36697224, 34937159, 34986804, 34220662, 32400930, 34380746, 31521395, 32358219, 31912665) (less)
Likely pathogenic (Mar 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV000892473.26 First in ClinVar: Mar 31, 2019 Last updated: Oct 20, 2024	Comment: SNORD118: PM3:Strong, PM2:Supporting, PS3:Supporting Number of individuals with the variant: 9
Pathogenic (Oct 10, 2016)	no assertion criteria provided Method: literature only	LEUKOENCEPHALOPATHY, BRAIN CALCIFICATIONS, AND CYSTS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000322754.1 First in ClinVar: Oct 14, 2016 Last updated: Oct 14, 2016	Publications: PubMed (1) PubMed: 27571260 Comment on evidence: For discussion of the ter9C-T transition (n.9C-T, NR_033294.1) in the SNORD118 gene that was found in compound heterozygous state in patients with leukoencephalopathy, brain calcifications, … (more) For discussion of the ter9C-T transition (n.9C-T, NR_033294.1) in the SNORD118 gene that was found in compound heterozygous state in patients with leukoencephalopathy, brain calcifications, and cysts (LCC; 614561) by Jenkinson et al. (2016), see 616663.0005. (less)
Pathogenic (Apr 06, 2020)	no assertion criteria provided Method: clinical testing	Leukoencephalopathy, brain calcifications, and cysts Affected status: yes Allele origin: germline	Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine Accession: SCV001364099.1 First in ClinVar: Jun 27, 2020 Last updated: Jun 27, 2020	Publications: PubMed (1) PubMed: 31521395 Number of individuals with the variant: 12

Comment:

Functional studies provide conflicting evidence, with one study suggesting this variant alters processing of the precursor U8 snoRNAs while another study suggests this variant is functional (PMID: 27571260, 32359472); Variant in a snoRNA that alters a C:G Watson-Crick base pair to a U:G wobble base pair in the 3' extension (PMID: 32359472); This variant is associated with the following publications: (PMID: 32359472, 33029936, 27571260, 34426522, 37761957, 36697224, 34937159, 34986804, 34220662, 32400930, 34380746, 31521395, 32358219, 31912665)

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review.	Osman O	Revue neurologique	2020	PMID: 31521395
Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.	Jenkinson EM	Nature genetics	2016	PMID: 27571260

Text-mined citations for rs201787275 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_183065.4(TMEM107):c.*759C>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs201787275 ...