NM_000434.4(NEU1):c.544A>G (p.Ser182Gly) AND Sialidosis

Clinical significance:Pathogenic (Last evaluated: Sep 26, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000781657.1

Allele description [Variation Report for NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)]

NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)

Gene:
NEU1:neuraminidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.33
Genomic location:
Preferred name:
NM_000434.4(NEU1):c.544A>G (p.Ser182Gly)
HGVS:
  • NC_000006.12:g.31861259T>C
  • NG_008201.1:g.6674A>G
  • NG_023058.1:g.22788A>G
  • NM_000434.4:c.544A>GMANE SELECT
  • NP_000425.1:p.Ser182Gly
  • NC_000006.11:g.31829036T>C
  • NM_000434.3:c.544A>G
Protein change:
S182G
Links:
dbSNP: rs398123392
NCBI 1000 Genomes Browser:
rs398123392
Molecular consequence:
  • NM_000434.4:c.544A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sialidosis
Identifiers:
MONDO: MONDO:0017734; MedGen: C0268226; Orphanet: 309294

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000919869Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Sep 26, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

First report of two Taiwanese siblings with sialidosis type I: a 10-year follow-up study.

Chen CM, Lai SC, Chen IC, Hsu KC, Lyu RK, Ro LS, Chang HS.

J Neurol Sci. 2006 Aug 15;247(1):65-9. Epub 2006 May 18.

PubMed [citation]
PMID:
16712870

Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex.

Lukong KE, Elsliger MA, Chang Y, Richard C, Thomas G, Carey W, Tylki-Szymanska A, Czartoryska B, Buchholz T, Criado GR, Palmeri S, Pshezhetsky AV.

Hum Mol Genet. 2000 Apr 12;9(7):1075-85.

PubMed [citation]
PMID:
10767332

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919869.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: NEU1 c.544A>G (p.Ser182Gly) results in a non-conservative amino acid change located in the Sialidase domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.5e-05 in 241352 control chromosomes (gnomAD and publications). This frequency is not significantly higher than expected for a pathogenic variant in NEU1 causing Sialidosis (9.5e-05 vs 0.0011), allowing no conclusion about variant significance. c.544A>G has been reported in the literature in multiple individuals affected with Sialidosis (Chen_2006, Lukong_2000). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Chen_2006, Lukong_2000). The most pronounced variant effect results in <10% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Jun 14, 2021

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