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NM_014363.6(SACS):c.9249del (p.Leu3083_Ile3084insTer) AND Spastic paraplegia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 6, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001043420.8

Allele description [Variation Report for NM_014363.6(SACS):c.9249del (p.Leu3083_Ile3084insTer)]

NM_014363.6(SACS):c.9249del (p.Leu3083_Ile3084insTer)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.9249del (p.Leu3083_Ile3084insTer)
HGVS:
  • NC_000013.11:g.23334628del
  • NG_012342.1:g.104076del
  • NM_001278055.2:c.8808del
  • NM_014363.6:c.9249delMANE SELECT
  • NP_001264984.1:p.Leu2936_Ile2937insTer
  • NP_055178.3:p.Leu3083_Ile3084insTer
  • NC_000013.10:g.23908766del
  • NC_000013.10:g.23908767del
  • NM_014363.5:c.9249del
Links:
dbSNP: rs1868403104
NCBI 1000 Genomes Browser:
rs1868403104
Molecular consequence:
  • NM_001278055.2:c.8808del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.9249del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Spastic paraplegia
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001207166Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 6, 2019) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.

Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B.

Neurogenetics. 2008 Jul;9(3):207-14. doi: 10.1007/s10048-008-0131-7. Epub 2008 May 9. Erratum in: Neurogenetics. 2009 Feb;10(1):87.

PubMed [citation]
PMID:
18465152
PMCID:
PMC2441586

Novel mutations in the sacsin gene in ataxia patients from Maritime Canada.

Guernsey DL, Dubé MP, Jiang H, Asselin G, Blowers S, Evans S, Ferguson M, Macgillivray C, Matsuoka M, Nightingale M, Rideout A, Delatycki M, Orr A, Ludman M, Dooley J, Riddell C, Samuels ME.

J Neurol Sci. 2010 Jan 15;288(1-2):79-87. doi: 10.1016/j.jns.2009.09.034. Epub 2009 Nov 4.

PubMed [citation]
PMID:
19892370
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001207166.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Arg3903* and p.Arg3636*) have been determined to be pathogenic (PMID: 18465152, 19892370, 21745802, 29915382). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with SACS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SACS gene (p.Ile3084*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1496 amino acids of the SACS protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024