NM_014363.6(SACS):c.9088_9089dup (p.Leu3030fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 16, 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:: RCV002523868.3

Allele description [Variation Report for NM_014363.6(SACS):c.9088_9089dup (p.Leu3030fs)]

NM_014363.6(SACS):c.9088_9089dup (p.Leu3030fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.9088_9089dup (p.Leu3030fs)

HGVS:

NC_000013.11:g.23334788_23334789dup
NG_012342.1:g.103915_103916dup
NM_001278055.2:c.8647_8648dup
NM_014363.6:c.9088_9089dupMANE SELECT
NP_001264984.1:p.Leu2883fs
NP_055178.3:p.Leu3030fs
NC_000013.10:g.23908925_23908926insAA
NC_000013.10:g.23908927_23908928dup
NM_014363.4:c.9088_9089dupTT

Protein change:

L2883fs

Links:

dbSNP: rs1057517060

NCBI 1000 Genomes Browser:

rs1057517060

Molecular consequence:

NM_001278055.2:c.8647_8648dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.9088_9089dup - 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
SCV003324407	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 16, 2022)	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

SCV003324407

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 16, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV003324407.2

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SACS protein in which other variant(s) (p.Leu3102*) have been determined to be pathogenic (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. ClinVar contains an entry for this variant (Variation ID: 371167). This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu3030Phefs*23) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1550 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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