NM_014363.6(SACS):c.4782C>G (p.Asp1594Glu) AND Spastic paraplegia

Clinical significance:Uncertain significance (Last evaluated: Feb 11, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001223402.2

Allele description [Variation Report for NM_014363.6(SACS):c.4782C>G (p.Asp1594Glu)]

NM_014363.6(SACS):c.4782C>G (p.Asp1594Glu)

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.4782C>G (p.Asp1594Glu)
HGVS:
  • NC_000013.11:g.23339094G>C
  • NG_012342.1:g.99609C>G
  • NM_001278055.2:c.4341C>G
  • NM_014363.6:c.4782C>GMANE SELECT
  • NP_001264984.1:p.Asp1447Glu
  • NP_055178.3:p.Asp1594Glu
  • NC_000013.10:g.23913233G>C
  • NM_014363.5:c.4782C>G
Protein change:
D1447E
Links:
Molecular consequence:
  • NM_001278055.2:c.4341C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014363.6:c.4782C>G - 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
SCV001395551Invitaecriteria provided, single submitter
Uncertain significance
(Feb 11, 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, SCV001395551.2

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

Description

This sequence change replaces aspartic acid with glutamic acid at codon 1594 of the SACS protein (p.Asp1594Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). 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: Oct 8, 2021

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