NM_014363.6(SACS):c.3328dup (p.Ile1110fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 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:: RCV001850406.6

Allele description [Variation Report for NM_014363.6(SACS):c.3328dup (p.Ile1110fs)]

NM_014363.6(SACS):c.3328dup (p.Ile1110fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.3328dup (p.Ile1110fs)

HGVS:

NC_000013.11:g.23340555dup
NG_012342.1:g.98155dup
NM_001278055.2:c.2887dup
NM_014363.6:c.3328dupMANE SELECT
NP_001264984.1:p.Ile963fs
NP_055178.3:p.Ile1110fs
NC_000013.10:g.23914686_23914687insT
NC_000013.10:g.23914694dup
NM_014363.4:c.3328dupA

Protein change:

I1110fs

Links:

OMIM: 604490.0005; dbSNP: rs770866403

NCBI 1000 Genomes Browser:

rs770866403

Molecular consequence:

NM_001278055.2:c.2887dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.3328dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Gm41898 predicted gene, 41898 [Mus musculus]
Gm41898 predicted gene, 41898 [Mus musculus]
Gene ID:105246637

Gene
Gm41898 AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002240128	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12873855, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002240128

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 2023)

germline

clinical testing

PubMed (2)
[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

Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.

El Euch-Fayache G, Lalani I, Amouri R, Turki I, Ouahchi K, Hung WY, Belal S, Siddique T, Hentati F.

Arch Neurol. 2003 Jul;60(7):982-8.

PubMed [citation]

PMID:: 12873855

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002240128.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189157). This variant is also known as 1155insA. This premature translational stop signal has been observed in individual(s) with autosomal recessive cerebellar ataxia (PMID: 12873855). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ile1110Asnfs*2) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3470 amino acid(s) of the SACS protein.

#	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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