NM_005476.7(GNE):c.1798G>A (p.Ala600Thr) AND GNE myopathy

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Mar 19, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000675176.5

Allele description [Variation Report for NM_005476.7(GNE):c.1798G>A (p.Ala600Thr)]

NM_005476.7(GNE):c.1798G>A (p.Ala600Thr)

Gene:

GNE:glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_005476.7(GNE):c.1798G>A (p.Ala600Thr)

HGVS:

NC_000009.12:g.36219856C>T
NG_008246.1:g.62189G>A
NM_001128227.3:c.1891G>A
NM_001190383.3:c.1576G>A
NM_001190384.3:c.1468G>A
NM_001190388.2:c.1621G>A
NM_001374797.1:c.1645G>A
NM_001374798.1:c.1621G>A
NM_005476.7:c.1798G>AMANE SELECT
NP_001121699.1:p.Ala631Thr
NP_001177312.1:p.Ala526Thr
NP_001177313.1:p.Ala490Thr
NP_001177317.2:p.Ala541Thr
NP_001361726.1:p.Ala549Thr
NP_001361727.1:p.Ala541Thr
NP_005467.1:p.Ala600Thr
LRG_1197t1:c.1891G>A
LRG_1197t2:c.1798G>A
LRG_1197:g.62189G>A
LRG_1197p1:p.Ala631Thr
LRG_1197p2:p.Ala600Thr
NC_000009.11:g.36219853C>T
NM_001128227.2:c.1891G>A

Protein change:

A490T

Links:

dbSNP: rs387906347

NCBI 1000 Genomes Browser:

rs387906347

Molecular consequence:

NM_001128227.3:c.1891G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190383.3:c.1576G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190384.3:c.1468G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190388.2:c.1621G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374797.1:c.1645G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374798.1:c.1621G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005476.7:c.1798G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: GNE myopathy (NM)
Synonyms:: Nonaka myopathy; Nonaka distal myopathy; INCLUSION BODY MYOPATHY, HEREDITARY, AUTOSOMAL RECESSIVE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011603; MedGen: C1853926; Orphanet: 602; OMIM: 605820

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000800804	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Feb 23, 2018)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15146476, 11528398, 18555875, 16503651 Citation Link,
SCV001458431	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Sep 16, 2020)	germline	clinical testing
SCV004191647	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 19, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004803576	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11528398, 16503651, 15146476, 19596068 Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[Distal myopathy due to mutations of GNE gene: clinical spectrum and diagnosis].

Béhin A, Dubourg O, Laforêt P, Pêcheux C, Bernard R, Lévy N, Eymard B.

Rev Neurol (Paris). 2008 May;164(5):434-43. doi: 10.1016/j.neurol.2008.02.040. Epub 2008 Apr 15. French.

PubMed [citation]

PMID:: 18555875

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000800804.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001458431.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004191647.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004803576.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: GNE c.1891G>A (p.Ala631Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251472 control chromosomes (gnomAD). c.1891G>A has been reported in the literature in individuals affected with hereditary inclusion-body myopathy (examples: Broccolini_2004, Huizing_2003, and Eisenberg_2001). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in >50%-90% of normal activity (Penner_2006). A different variant (c.1892C>T/p.Ala631Val) affecting this residue has been classified pathogenic in ClinVar (CV ID 6035). The following publications have been ascertained in the context of this evaluation (PMID: 15146476, 11528398, 19596068, 16503651). ClinVar contains an entry for this variant (Variation ID: 286014). Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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