NM_014363.6(SACS):c.1720C>T (p.Gln574Ter) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 10, 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:: RCV002581827.3

Allele description [Variation Report for NM_014363.6(SACS):c.1720C>T (p.Gln574Ter)]

NM_014363.6(SACS):c.1720C>T (p.Gln574Ter)

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.1720C>T (p.Gln574Ter)

HGVS:

NC_000013.11:g.23354892G>A
NG_012342.1:g.83811C>T
NM_001278055.2:c.1279C>T
NM_014363.6:c.1720C>TMANE SELECT
NP_001264984.1:p.Gln427Ter
NP_055178.3:p.Gln574Ter
NC_000013.10:g.23929031G>A

Protein change:

Q427*

Molecular consequence:

NM_001278055.2:c.1279C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014363.6:c.1720C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003487438	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 10, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18465152, 20876471, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003487438

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 10, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Mutations in SACS cause atypical and late-onset forms of ARSACS.

Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P.

Neurology. 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c.

PubMed [citation]

PMID:: 20876471

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003487438.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln574*) in the SACS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SACS are known to be pathogenic (PMID: 18465152, 20876471). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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