NM_014363.6(SACS):c.7539_7540del (p.Cys2514fs) AND Charlevoix-Saguenay spastic ataxia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 14, 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:: RCV003448439.2

Allele description [Variation Report for NM_014363.6(SACS):c.7539_7540del (p.Cys2514fs)]

NM_014363.6(SACS):c.7539_7540del (p.Cys2514fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.7539_7540del (p.Cys2514fs)

HGVS:

NC_000013.11:g.23336337_23336338del
NG_012342.1:g.102366_102367del
NM_001278055.2:c.7098_7099del
NM_014363.6:c.7539_7540delMANE SELECT
NP_001264984.1:p.Cys2367fs
NP_055178.3:p.Cys2514fs
NC_000013.10:g.23910475_23910476del
NC_000013.10:g.23910476_23910477del

Protein change:

C2367fs

Links:

dbSNP: rs1467848128

NCBI 1000 Genomes Browser:

rs1467848128

Molecular consequence:

NM_001278055.2:c.7098_7099del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.7539_7540del - 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

Recent activity

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Mus musculus chemokine (C-C motif) receptor 3 (Ccr3), mRNA
Mus musculus chemokine (C-C motif) receptor 3 (Ccr3), mRNA
gi|142378618|ref|NM_009914.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004176525	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004176525

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 14, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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 Neuberg Centre For Genomic Medicine, NCGM, SCV004176525.1

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

Description

The frame shift c.7539_7540del (p.Cys2514PhefsTer19) variant in SACS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0003%) in the gnomAD Exomes and novel in 1000. The variant has been reported as Pathogenic in ClinVar database, but no details are available for independent assessment. This variant causes a frameshift starting with codon Cysteine 2514, changes this amino acid to Phenylalanine residue, and creates a premature Stop codon at position 19 of the new reading frame, denoted p.Cys2514PhefsTer19. Loss of function variants have been previously reported to be disease causing. However, since this variant is present in the last exon, further studies will be required to prove protein truncation. For these reasons, this variant has been classified as Uncertain Significance.

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

Last Updated: Sep 29, 2024

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