VCV000374891.1 - ClinVar

NM_001303250.3(SLC25A46):c.10+526_11-1368delinsGGCCGGGCGCG

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

NM_001303250.3(SLC25A46):c.10+526_11-1368delinsGGCCGGGCGCG

Variation ID: 374891 Accession: VCV000374891.1

Type and length

Indel, 1,907 bp

Location

Cytogenetic: 5q22.1 5: 110074474-110076380 (GRCh37) [ NCBI UCSC ] 5: 110738773-110740679 (GRCh38) [ 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	Jan 23, 2017	Jan 23, 2017	Jan 14, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_001303250.3:c.10+526_11-1368delinsGGCCGGGCGCG		intron variant
NC_000005.10:g.110738773_110740679delinsGGCCGGGCGCG
NC_000005.9:g.110074474_110076380delinsGGCCGGGCGCG
NG_051334.1:g.5638_7544delinsGGCCGGGCGCG
NG_105472.1:g.1_436delinsGGCCGGGCGCG
NG_173789.1:g.1_327delinsGGCCGGGC
NG_173790.1:g.1_270delinsGGCCGGGCGCG
LRG_1091:g.5638_7544delinsGGCCGGGCGCG

... more HGVS ... less HGVS

Protein change

Other names

1.897-KB DEL

Canonical SPDI

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: 610826.0008 VarSome

Comment on variant

NCBI staff provided an HGVS expression for OMIM allelic variant 610826.0008 from the sequence across the breakpoint in Supplementary Figure 1B in the paper by Wan et al., 2016 (PubMed 27543974).

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.
LOC129994343	-	-	-	GRCh38	-	18
LOC129994344	-	-	-	GRCh38	-	17
SLC25A46		-	-	GRCh38 GRCh37	378	421
TMEM232		-	-	GRCh38 GRCh37	45	89

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.
Neuropathy, hereditary motor and sensory, type 6B	Pathogenic (1)	no assertion criteria provided	Jan 14, 2017	RCV000415521.1

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 (Jan 14, 2017)	no assertion criteria provided Method: literature only	NEUROPATHY, HEREDITARY MOTOR AND SENSORY, TYPE VIB Affected status: not provided Allele origin: germline	OMIM Accession: SCV000493977.1 First in ClinVar: Jan 23, 2017 Last updated: Jan 23, 2017	Publications: PubMed (1) PubMed: 27543974 Comment on evidence: In 2 sibs, born of consanguineous parents, with a severe form of hereditary motor and sensory neuropathy type VIB (HMSN6B; 616505) resulting in death in … (more) In 2 sibs, born of consanguineous parents, with a severe form of hereditary motor and sensory neuropathy type VIB (HMSN6B; 616505) resulting in death in infancy, Wan et al. (2016) identified a homozygous 1.897-kb deletion in exon 1 of the SLC25A46 gene, resulting in the elimination of the initiation codon ATG for the longest transcript. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The mutation was predicted to result in an N-terminal truncated protein and a loss of function. (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
Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia.	Wan J	Brain : a journal of neurology	2016	PMID: 27543974

Text-mined citations for this variant ...

Record last updated Dec 07, 2024

ClinVar Genomic variation as it relates to human health

NM_001303250.3(SLC25A46):c.10+526_11-1368delinsGGCCGGGCGCG

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...