NM_005476.7(GNE):c.1414A>G (p.Ile472Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 2021
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:: RCV003068581.2

Allele description [Variation Report for NM_005476.7(GNE):c.1414A>G (p.Ile472Val)]

NM_005476.7(GNE):c.1414A>G (p.Ile472Val)

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.1414A>G (p.Ile472Val)

HGVS:

NC_000009.12:g.36222996T>C
NG_008246.1:g.59049A>G
NM_001128227.3:c.1507A>G
NM_001190383.3:c.1411+377A>G
NM_001190384.3:c.1084A>G
NM_001190388.2:c.1237A>G
NM_001374797.1:c.1261A>G
NM_001374798.1:c.1237A>G
NM_005476.7:c.1414A>GMANE SELECT
NP_001121699.1:p.Ile503Val
NP_001177313.1:p.Ile362Val
NP_001177317.2:p.Ile413Val
NP_001361726.1:p.Ile421Val
NP_001361727.1:p.Ile413Val
NP_005467.1:p.Ile472Val
LRG_1197t1:c.1507A>G
LRG_1197t2:c.1414A>G
LRG_1197:g.59049A>G
LRG_1197p1:p.Ile503Val
LRG_1197p2:p.Ile472Val
NC_000009.11:g.36222993T>C

Protein change:

I362V

Molecular consequence:

NM_001190383.3:c.1411+377A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001128227.3:c.1507A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001190384.3:c.1084A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001190388.2:c.1237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374797.1:c.1261A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374798.1:c.1237A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005476.7:c.1414A>G - 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

Name:: Sialuria
Synonyms:: Sialic Acid Storage Disease; Sialuria, French type
Identifiers:: MONDO: MONDO:0010028; MedGen: C0342853; Orphanet: 3166; OMIM: 269921

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003454878	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 17, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12913203, 14707127, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003454878

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 17, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

GNE mutations causing distal myopathy with rimmed vacuoles with inflammation.

Yabe I, Higashi T, Kikuchi S, Sasaki H, Fukazawa T, Yoshida K, Tashiro K.

Neurology. 2003 Aug 12;61(3):384-6.

PubMed [citation]

PMID:: 12913203

Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase activity and sialylation in distal myopathy with rimmed vacuoles.

Noguchi S, Keira Y, Murayama K, Ogawa M, Fujita M, Kawahara G, Oya Y, Imazawa M, Goto Y, Hayashi YK, Nonaka I, Nishino I.

J Biol Chem. 2004 Mar 19;279(12):11402-7. Epub 2004 Jan 5.

PubMed [citation]

PMID:: 14707127

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003454878.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces isoleucine with valine at codon 503 of the GNE protein (p.Ile503Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GNE-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant disrupts the p.Ile503 amino acid residue in GNE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12913203, 14707127). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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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