NM_014363.6(SACS):c.5428C>T (p.Gln1810Ter) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Dec 27, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001039830.1

Allele description [Variation Report for NM_014363.6(SACS):c.5428C>T (p.Gln1810Ter)]

NM_014363.6(SACS):c.5428C>T (p.Gln1810Ter)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.5428C>T (p.Gln1810Ter)
HGVS:
  • NC_000013.11:g.23338448G>A
  • NG_012342.1:g.100255C>T
  • NM_001278055.2:c.4987C>T
  • NM_014363.6:c.5428C>TMANE SELECT
  • NP_001264984.1:p.Gln1663Ter
  • NP_055178.3:p.Gln1810Ter
  • NC_000013.10:g.23912587G>A
  • NM_014363.4:c.5428C>T
  • NM_014363.5:c.5428C>T
Protein change:
Q1663*
Molecular consequence:
  • NM_001278055.2:c.4987C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014363.6:c.5428C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Spastic paraplegia
Synonyms:
Spastic paraplegia, lower limb
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001203378Invitaecriteria provided, single submitter
Pathogenic
(Dec 27, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

A reduction in Drp1-mediated fission compromises mitochondrial health in autosomal recessive spastic ataxia of Charlevoix Saguenay.

Bradshaw TY, Romano LE, Duncan EJ, Nethisinghe S, Abeti R, Michael GJ, Giunti P, Vermeer S, Chapple JP.

Hum Mol Genet. 2016 Aug 1;25(15):3232-3244. doi: 10.1093/hmg/ddw173. Epub 2016 Jun 10.

PubMed [citation]
PMID:
27288452
PMCID:
PMC5179924
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001203378.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change results in a premature translational stop signal in the SACS gene (p.Gln1810*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2,770 amino acids of the SACS protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SACS-related conditions. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Gln4054*) have been determined to be pathogenic (PMID: 18465152, 27288452). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

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