NM_014363.6(SACS):c.9561_9564del (p.Leu3187_Phe3188insTer) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Jul 11, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000470443.1

Allele description [Variation Report for NM_014363.6(SACS):c.9561_9564del (p.Leu3187_Phe3188insTer)]

NM_014363.6(SACS):c.9561_9564del (p.Leu3187_Phe3188insTer)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.9561_9564del (p.Leu3187_Phe3188insTer)
HGVS:
  • NC_000013.11:g.23334314_23334317del
  • NG_012342.1:g.104388_104391del
  • NM_001278055.2:c.9120_9123del
  • NM_014363.6:c.9561_9564delMANE SELECT
  • NP_001264984.1:p.Leu3040_Phe3041insTer
  • NP_055178.3:p.Leu3187_Phe3188insTer
  • NC_000013.10:g.23908453_23908456del
  • NM_014363.4:c.9561_9564del
  • NM_014363.5:c.9561_9564delGTTT
Links:
dbSNP: rs1060503431
NCBI 1000 Genomes Browser:
rs1060503431
Molecular consequence:
  • NM_001278055.2:c.9120_9123del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.9561_9564del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Spastic paraplegia
Synonyms:
Spastic paraplegia, lower limb
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000552969Invitaecriteria provided, single submitter
Pathogenic
(Jul 11, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000552969.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change deletes 4 nucleotides from exon 10 of the SACS mRNA (c.9561_9564delGTTT), causing a frameshift at codon 3188. This creates a premature translational stop signal in the last exon of the SACS mRNA (p.Phe3188*). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated SACS protein. While this particular variant has not been reported in the literature, truncating variants in SACS are known to be pathogenic (PMID: 18465152). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

Support Center