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NM_014363.6(SACS):c.11092C>T (p.Gln3698Ter) AND Charlevoix-Saguenay spastic ataxia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 25, 2023
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:
RCV002790005.2

Allele description [Variation Report for NM_014363.6(SACS):c.11092C>T (p.Gln3698Ter)]

NM_014363.6(SACS):c.11092C>T (p.Gln3698Ter)

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.11092C>T (p.Gln3698Ter)
Other names:
NM_001278055.2:c.10651C>T
HGVS:
  • NC_000013.11:g.23332784G>A
  • NG_012342.1:g.105919C>T
  • NM_001278055.2:c.10651C>T
  • NM_014363.6:c.11092C>TMANE SELECT
  • NP_001264984.1:p.Gln3551Ter
  • NP_055178.3:p.Gln3698Ter
  • NC_000013.10:g.23906923G>A
Protein change:
Q3551*
Links:
dbSNP: rs1883571494
NCBI 1000 Genomes Browser:
rs1883571494
Molecular consequence:
  • NM_001278055.2:c.10651C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014363.6:c.11092C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Charlevoix-Saguenay spastic ataxia (SACS)
Synonyms:
Autosomal recessive spastic ataxia of Charlevoix-Saguenay; Spastic ataxia of Charlevoix-Saguenay; SPASTIC ATAXIA 6, AUTOSOMAL RECESSIVE
Identifiers:
MONDO: MONDO:0010041; MedGen: C1849140; Orphanet: 98; OMIM: 270550

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003761330Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jan 25, 2023) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761330.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The homozygous p.Gln3698Ter variant in SACS was identified by our study in three siblings with spastic ataxia. The p.Gln3698Ter variant in SACS has not been previously reported in individuals with spastic ataxia of the Charlevoix-Saguenay type. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 3698. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the SACS gene is an established disease mechanism of autosomal recessive spastic ataxia of the Charlevoix-Saguenay type. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive spastic ataxia of the Charlevoix-Saguenay type. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM3_Supporting (Richards 2015).

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

Last Updated: Mar 30, 2024