ClinVar Genomic variation as it relates to human health
NM_005476.7(GNE):c.38G>C (p.Cys13Ser)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005476.7(GNE):c.38G>C (p.Cys13Ser)
Variation ID: 496947 Accession: VCV000496947.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9p13.3 9: 36249318 (GRCh38) [ NCBI UCSC ] 9: 36249315 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 2, 2018 Jun 17, 2024 Dec 6, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005476.7:c.38G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005467.1:p.Cys13Ser missense NM_001128227.3:c.131G>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001121699.1:p.Cys44Ser missense NM_001190383.3:c.38G>C NP_001177312.1:p.Cys13Ser missense NM_001190384.3:c.-13-2836G>C intron variant NM_001190388.2:c.-13-2836G>C intron variant NM_001374797.1:c.38G>C NP_001361726.1:p.Cys13Ser missense NM_001374798.1:c.-13-2836G>C intron variant NC_000009.12:g.36249318C>G NC_000009.11:g.36249315C>G NG_008246.1:g.32727G>C LRG_1197:g.32727G>C LRG_1197t1:c.131G>C LRG_1197p1:p.Cys44Ser LRG_1197t2:c.38G>C LRG_1197p2:p.Cys13Ser - Protein change
- C13S, C44S
- Other names
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- Canonical SPDI
- NC_000009.12:36249317:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GNE | - | - |
GRCh38 GRCh37 |
1039 | 1115 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 15, 2016 | RCV000594728.4 | |
Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Dec 6, 2023 | RCV000755013.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 9, 2023 | RCV001853994.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Nov 15, 2016)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000700792.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Number of individuals with the variant: 14
Sex: mixed
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Pathogenic
(Aug 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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GNE myopathy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004037813.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
Comment:
Variant summary: GNE c.131G>C (p.Cys44Ser), also referred to as c.89G>C (p.Cys13Ser) in the literature, results in a non-conservative amino acid change located in the UDP-N-acetylglucosamine … (more)
Variant summary: GNE c.131G>C (p.Cys44Ser), also referred to as c.89G>C (p.Cys13Ser) in the literature, results in a non-conservative amino acid change located in the UDP-N-acetylglucosamine 2-epimerase domain (IPR003331) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251418 control chromosomes (gnomAD). c.131G>C has been reported in the literature as a biallelic genotype in multiple individuals affected with Inclusion Body Myopathy 2/Distal Myopathy with Rimmed Vacuoles (e.g. Saito_2004, Noguchi_2004, Sim_2013). 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 in vitro and found the UDP-GlcNAc 2-epimerase activity of the variant was approximately 20% of the wild type protein (e.g. Noguchi_2004). The following publications have been ascertained in the context of this evaluation (PMID: 14707127, 14733963, 23549799). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Apr 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Sialuria
GNE myopathy
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002240531.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNE function (PMID: 14707127). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GNE function (PMID: 14707127). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GNE protein function. ClinVar contains an entry for this variant (Variation ID: 496947). This missense change has been observed in individuals with autosomal recessive distal myopathy with rimmed vacuoles (DMRV) (PMID: 14707127, 14733962, 22507750, 27363342, 28403181, 30390020, 31286697). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 44 of the GNE protein (p.Cys44Ser). (less)
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Pathogenic
(Dec 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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GNE myopathy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004199391.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Feb 11, 2019)
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no assertion criteria provided
Method: research
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GNE myopathy
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Department of Rehabilitation Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
Accession: SCV000882745.1
First in ClinVar: Feb 17, 2019 Last updated: Feb 17, 2019 |
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Pathogenic
(Jun 27, 2019)
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no assertion criteria provided
Method: clinical testing
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GNE myopathy
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132211.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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not provided
(-)
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no classification provided
Method: literature only
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GNE myopathy
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV001364089.2
First in ClinVar: Jun 22, 2020 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Progression of GNE Myopathy Based on the Patient-Reported Outcome. | Park YE | Journal of clinical neurology (Seoul, Korea) | 2019 | PMID: 31286697 |
GNE myopathy in Chinese population: hotspot and novel mutations. | Chen Y | Journal of human genetics | 2019 | PMID: 30390020 |
Mutational spectrum of Chinese LGMD patients by targeted next-generation sequencing. | Yu M | PloS one | 2017 | PMID: 28403181 |
Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders. | Park HJ | Clinical genetics | 2017 | PMID: 27363342 |
Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy. | Cerino M | Journal of neuromuscular diseases | 2015 | PMID: 27858732 |
Mutational spectrum and clinical features in 35 unrelated mainland Chinese patients with GNE myopathy. | Zhao J | Journal of the neurological sciences | 2015 | PMID: 25986339 |
Mutation update for GNE gene variants associated with GNE myopathy. | Celeste FV | Human mutation | 2014 | PMID: 24796702 |
Two recurrent mutations are associated with GNE myopathy in the North of Britain. | Chaouch A | Journal of neurology, neurosurgery, and psychiatry | 2014 | PMID: 24695763 |
Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy). | Cho A | Journal of neurology, neurosurgery, and psychiatry | 2014 | PMID: 24027297 |
Clinical characteristics and molecular genetic analysis of Korean patients with GNE myopathy. | Sim JE | Yonsei medical journal | 2013 | PMID: 23549799 |
Limb-girdle phenotype is frequent in patients with myopathy associated with GNE mutations. | Park YE | Journal of the neurological sciences | 2012 | PMID: 22883483 |
Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations. | Mori-Yoshimura M | Journal of the neurological sciences | 2012 | PMID: 22507750 |
Mutation analysis of the GNE gene in Korean patients with distal myopathy with rimmed vacuoles. | Kim BJ | Journal of human genetics | 2006 | PMID: 16372135 |
A Japanese patient with distal myopathy with rimmed vacuoles: missense mutations in the epimerase domain of the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene accompanied by hyposialylation of skeletal muscle glycoproteins. | Saito F | Neuromuscular disorders : NMD | 2004 | PMID: 14733963 |
Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles. | Noguchi S | The Journal of biological chemistry | 2004 | PMID: 14707127 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GNE | - | - | - | - |
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Text-mined citations for rs1209266607 ...
HelpRecord last updated Jun 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.