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NM_014363.5(SACS):c.8393C>A (p.Pro2798Gln) AND Spastic paraplegia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 5, 2017
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:
RCV000230214.2

Allele description

NM_014363.5(SACS):c.8393C>A (p.Pro2798Gln)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.5(SACS):c.8393C>A (p.Pro2798Gln)
HGVS:
  • NC_000013.11:g.23335483G>T
  • NG_012342.1:g.103220C>A
  • NM_014363.5:c.8393C>A
  • NP_055178.3:p.Pro2798Gln
  • NC_000013.10:g.23909622G>T
  • NM_014363.4:c.8393C>A
  • Q9NZJ4:p.Pro2798Gln
Protein change:
P2798Q
Links:
UniProtKB: Q9NZJ4#VAR_064814; dbSNP: rs140551762
GMAF:
0.0004(T), 140551762
NCBI 1000 Genomes Browser:
rs140551762
Allele Frequency:
0.00180(T)
Molecular consequence:
  • NM_014363.5:c.8393C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spastic paraplegia
Identifiers:
MedGen: C0037772

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000289962Invitae,
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 5, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Invitae,, SCV000289962.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This sequence change replaces proline with glutamine at codon 2798 of the SACS protein (p.Pro2798Gln). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and glutamine. This variant is present in population databases (rs140551762, ExAC 0.3%). This variant has been reported in individuals affected with progressive myoclonus epilepsies (PMID: 25401298, 27433545) and with late-onset forms of autosomal recessive spastic ataxia of Charlevoix-Saguenay (PMID: 20876471). ClinVar contains an entry for this variant (Variation ID: 212115). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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: Dec 15, 2017