NM_014363.6(SACS):c.12622C>T (p.Gln4208Ter) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Nov 9, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001232544.2

Allele description [Variation Report for NM_014363.6(SACS):c.12622C>T (p.Gln4208Ter)]

NM_014363.6(SACS):c.12622C>T (p.Gln4208Ter)

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.12622C>T (p.Gln4208Ter)
HGVS:
  • NC_000013.11:g.23331254G>A
  • NG_012342.1:g.107449C>T
  • NM_001278055.2:c.12181C>T
  • NM_014363.6:c.12622C>TMANE SELECT
  • NP_001264984.1:p.Gln4061Ter
  • NP_055178.3:p.Gln4208Ter
  • NC_000013.10:g.23905393G>A
  • NM_014363.4:c.12622C>T
  • NM_014363.5:c.12622C>T
Protein change:
Q4061*
Links:
dbSNP: rs1555249555
NCBI 1000 Genomes Browser:
rs1555249555
Molecular consequence:
  • NM_001278055.2:c.12181C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014363.6:c.12622C>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
SCV001405106Invitaecriteria provided, single submitter
Pathogenic
(Nov 9, 2019)
germlineclinical testing

PubMed (4)
[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

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum.

Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schüle R, Haack TB, Schöning M, Biskup S, Rudnik-Schöneborn S, Senderek J, Hoffmann KT, MacLeod P, Schwarz J, Bender B, Krüger S, Kreuz F, Bauer P, Schöls L.

Orphanet J Rare Dis. 2013 Mar 15;8:41. doi: 10.1186/1750-1172-8-41.

PubMed [citation]
PMID:
23497566
PMCID:
PMC3610264

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, et al.

Ann Neurol. 2015 Dec;78(6):871-86. doi: 10.1002/ana.24509. Epub 2015 Nov 14.

PubMed [citation]
PMID:
26288984
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001405106.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change results in a premature translational stop signal in the SACS gene (p.Gln4208*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 372 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. ClinVar contains an entry for this variant (Variation ID: 553524). This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Leu4303*, p.Glu4309*, p.Arg4325*, and p.Phe4352Leufs*11) have been determined to be pathogenic and/or reported in individuals affected with autosomal recessive spastic ataxia of Charlevoix-Saguenay (PMID: 23497566, 26288984, 16944349, Invitae). 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: Oct 8, 2021

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