NM_014363.6(SACS):c.8716C>T (p.Arg2906Ter) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Sep 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001386448.1

Allele description [Variation Report for NM_014363.6(SACS):c.8716C>T (p.Arg2906Ter)]

NM_014363.6(SACS):c.8716C>T (p.Arg2906Ter)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.8716C>T (p.Arg2906Ter)
HGVS:
  • NC_000013.11:g.23335160G>A
  • NG_012342.1:g.103543C>T
  • NM_001278055.2:c.8275C>T
  • NM_014363.6:c.8716C>TMANE SELECT
  • NP_001264984.1:p.Arg2759Ter
  • NP_055178.3:p.Arg2906Ter
  • NC_000013.10:g.23909299G>A
  • NM_014363.5:c.8716C>T
Protein change:
R2759*
Links:
dbSNP: rs750732115
NCBI 1000 Genomes Browser:
rs750732115
Molecular consequence:
  • NM_001278055.2:c.8275C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014363.6:c.8716C>T - nonsense - [Sequence Ontology: SO:0001587]
Functional consequence:
No function

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001586676Invitaecriteria provided, single submitter
Pathogenic
(Sep 13, 2020)
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, SCV001586676.1

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

Description

This sequence change results in a premature translational stop signal in the SACS gene (p.Arg2906*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1674 amino acids of the SACS protein. This variant is present in population databases (rs750732115, ExAC 0.003%). This variant has not been reported in the literature in individuals with SACS-related conditions. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Tyr4538*) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Jul 27, 2021

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