NM_014363.6(SACS):c.9233del (p.Asn3078fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 2018
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:: RCV000819911.7

Allele description [Variation Report for NM_014363.6(SACS):c.9233del (p.Asn3078fs)]

NM_014363.6(SACS):c.9233del (p.Asn3078fs)

Gene:

SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.9233del (p.Asn3078fs)

HGVS:

NC_000013.11:g.23334644del
NG_012342.1:g.104060del
NM_001278055.2:c.8792del
NM_014363.6:c.9233delMANE SELECT
NP_001264984.1:p.Asn2931fs
NP_055178.3:p.Asn3078fs
NC_000013.10:g.23908782del
NC_000013.10:g.23908783del
NM_014363.5:c.9233delA

Protein change:

N2931fs

Links:

dbSNP: rs1593125341

NCBI 1000 Genomes Browser:

rs1593125341

Molecular consequence:

NM_001278055.2:c.8792del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.9233del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000960598	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19892370, 21745802, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960598

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2018)

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

Novel mutations in the sacsin gene in ataxia patients from Maritime Canada.

Guernsey DL, Dubé MP, Jiang H, Asselin G, Blowers S, Evans S, Ferguson M, Macgillivray C, Matsuoka M, Nightingale M, Rideout A, Delatycki M, Orr A, Ludman M, Dooley J, Riddell C, Samuels ME.

J Neurol Sci. 2010 Jan 15;288(1-2):79-87. doi: 10.1016/j.jns.2009.09.034. Epub 2009 Nov 4.

PubMed [citation]

PMID:: 19892370

Autosomal recessive spastic ataxia of Charlevoix-Saguenay: compound heterozygotes for nonsense mutations of the SACS gene.

Narayanan V, Rice SG, Olfers SS, Sivakumar K.

J Child Neurol. 2011 Dec;26(12):1585-9. doi: 10.1177/0883073811412825. Epub 2011 Jul 10.

PubMed [citation]

PMID:: 21745802

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960598.4

#	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 results in a premature translational stop signal in the SACS gene (p.Asn3078Ilefs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1502 amino acids of the SACS protein. For these reasons, this variant has been classified as Pathogenic. A different truncation (p.Arg3903*) that lies downstream of this variant has been determined to be pathogenic (PMID: 19892370, 21745802). This suggests that deletion of this region of the SACS protein is causative of disease. This variant has not been reported in the literature in individuals with SACS-related disease. This variant is not present in population databases (ExAC no frequency).

#	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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