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NM_014363.6(SACS):c.12673_12677del (p.Tyr4225fs) AND Charlevoix-Saguenay spastic ataxia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 2, 2022
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:
RCV002471600.2

Allele description [Variation Report for NM_014363.6(SACS):c.12673_12677del (p.Tyr4225fs)]

NM_014363.6(SACS):c.12673_12677del (p.Tyr4225fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.12673_12677del (p.Tyr4225fs)
HGVS:
  • NC_000013.11:g.23331200_23331204del
  • NG_012342.1:g.107500_107504del
  • NM_001278055.2:c.12232_12236del
  • NM_014363.4:c.12673_12677delTATCA
  • NM_014363.6:c.12673_12677delMANE SELECT
  • NP_001264984.1:p.Tyr4078fs
  • NP_055178.3:p.Tyr4225fs
  • NC_000013.10:g.23905338_23905342del
  • NC_000013.10:g.23905339_23905343del
  • NM_014363.4:c.12673_12677del
  • NM_014363.5:c.12673_12677delTATCA
Protein change:
Y4078fs
Links:
dbSNP: rs775863207
NCBI 1000 Genomes Browser:
rs775863207
Molecular consequence:
  • NM_001278055.2:c.12232_12236del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.12673_12677del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002768989Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Feb 2, 2022) 		germlineclinical testing

PubMed (2)
[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

Autosomal recessive spastic ataxia of Charlevoix-Saguenay caused by novel mutations in SACS gene: A report of two Chinese families.

Wang Z, Song Y, Wang X, Li X, Xu F, Si L, Dong Y, Yao T, Zhu J, Lai H, Li W, Lin F, Huang H, Wang C.

Neurosci Lett. 2021 May 1;752:135831. doi: 10.1016/j.neulet.2021.135831. Epub 2021 Mar 18.

PubMed [citation]
PMID:
33746006

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002768989.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS) (MIM#270550). (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0253 - This variant is hemizygous. External laboratory reports this individual has a large deletion on the other allele. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 2 heterozygotes, 0 homozygotes). (SP) 0701 - Other variants predicted to result in a truncated protein and located downstream, therefore comparable to the one identified in this case, have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an individual with ARSACS (PMID: 33746006). (SP) 1201 - Variant detected in trans with a second pathogenic heterozygous variant (approximately 1.4Mb deletion that encompasses the SACS gene) in a recessive disease (analysis by an external laboratory) . (I) 1206 - This variant has been shown to be paternally inherited by an external laboratory. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: May 16, 2025