NM_014363.6(SACS):c.9251T>C (p.Ile3084Thr) AND Spastic paraplegia

Clinical significance:Uncertain significance (Last evaluated: Mar 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001240147.1

Allele description [Variation Report for NM_014363.6(SACS):c.9251T>C (p.Ile3084Thr)]

NM_014363.6(SACS):c.9251T>C (p.Ile3084Thr)

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.9251T>C (p.Ile3084Thr)
HGVS:
  • NC_000013.11:g.23334625A>G
  • NG_012342.1:g.104078T>C
  • NM_001278055.2:c.8810T>C
  • NM_014363.6:c.9251T>CMANE SELECT
  • NP_001264984.1:p.Ile2937Thr
  • NP_055178.3:p.Ile3084Thr
  • NC_000013.10:g.23908764A>G
  • NM_014363.5:c.9251T>C
  • p.Ile3084Thr
Protein change:
I2937T
Molecular consequence:
  • NM_001278055.2:c.8810T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014363.6:c.9251T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001413071Invitaecriteria provided, single submitter
Uncertain significance
(Mar 28, 2019)
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, SCV001413071.1

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

Description

This sequence change replaces isoleucine with threonine at codon 3084 of the SACS protein (p.Ile3084Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs149290718, ExAC 0.006%). This variant has not been reported in the literature in individuals with SACS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jun 14, 2021

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