NM_014363.6(SACS):c.3356del (p.Pro1119fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 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:: RCV001383371.5

Allele description [Variation Report for NM_014363.6(SACS):c.3356del (p.Pro1119fs)]

NM_014363.6(SACS):c.3356del (p.Pro1119fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.3356del (p.Pro1119fs)

HGVS:

NC_000013.11:g.23340521del
NG_012342.1:g.98183del
NM_001278055.2:c.2915del
NM_014363.6:c.3356delMANE SELECT
NP_001264984.1:p.Pro972fs
NP_055178.3:p.Pro1119fs
NC_000013.10:g.23914659del
NC_000013.10:g.23914660del
NM_014363.4:c.3356delC

Protein change:

P1119fs

Links:

dbSNP: rs1057517039

NCBI 1000 Genomes Browser:

rs1057517039

Molecular consequence:

NM_001278055.2:c.2915del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.3356del - 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
SCV001582494	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2023)	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

SCV001582494

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2023)

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, SCV001582494.4

#	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 creates a premature translational stop signal (p.Pro1119Leufs*7) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3461 amino acid(s) of the SACS protein. This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SACS-related conditions. ClinVar contains an entry for this variant (Variation ID: 371143). This variant disrupts a region of the SACS protein in which other variant(s) (p.Leu4303*, p.Arg3903*) have been determined to be pathogenic (PMID: 19892370, 21745802; Invitae). 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.

#	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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