U.S. flag

An official website of the United States government

NM_014363.6(SACS):c.8911C>T (p.Gln2971Ter) AND Spastic paraplegia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 24, 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:
RCV003752144.2

Allele description [Variation Report for NM_014363.6(SACS):c.8911C>T (p.Gln2971Ter)]

NM_014363.6(SACS):c.8911C>T (p.Gln2971Ter)

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.8911C>T (p.Gln2971Ter)
HGVS:
  • NC_000013.11:g.23334965G>A
  • NG_012342.1:g.103738C>T
  • NM_001278055.2:c.8470C>T
  • NM_014363.6:c.8911C>TMANE SELECT
  • NP_001264984.1:p.Gln2824Ter
  • NP_055178.3:p.Gln2971Ter
  • NC_000013.10:g.23909104G>A
Protein change:
Q2824*
Molecular consequence:
  • NM_001278055.2:c.8470C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014363.6:c.8911C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

Recent activity

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004501790Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Feb 24, 2023)
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

Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey.

Richter AM, Ozgul RK, Poisson VC, Topaloglu H.

Neurogenetics. 2004 Sep;5(3):165-70. Epub 2004 May 20.

PubMed [citation]
PMID:
15156359

Structural basis of defects in the sacsin HEPN domain responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Kozlov G, Denisov AY, Girard M, Dicaire MJ, Hamlin J, McPherson PS, Brais B, Gehring K.

J Biol Chem. 2011 Jun 10;286(23):20407-12. doi: 10.1074/jbc.M111.232884. Epub 2011 Apr 20.

PubMed [citation]
PMID:
21507954
PMCID:
PMC3121481
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004501790.1

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

Description

This sequence change creates a premature translational stop signal (p.Gln2971*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1609 amino acid(s) of the SACS protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp) have been determined to be pathogenic (PMID: 15156359, 21507954). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Sep 29, 2024