NM_005476.7(GNE):c.1442G>A (p.Arg481Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 2022
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:: RCV000531870.7

Allele description [Variation Report for NM_005476.7(GNE):c.1442G>A (p.Arg481Gln)]

NM_005476.7(GNE):c.1442G>A (p.Arg481Gln)

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.1442G>A (p.Arg481Gln)

HGVS:

NC_000009.12:g.36222968C>T
NG_008246.1:g.59077G>A
NM_001128227.3:c.1535G>A
NM_001190383.3:c.1411+405G>A
NM_001190384.3:c.1112G>A
NM_001190388.2:c.1265G>A
NM_001374797.1:c.1289G>A
NM_001374798.1:c.1265G>A
NM_005476.7:c.1442G>AMANE SELECT
NP_001121699.1:p.Arg512Gln
NP_001177313.1:p.Arg371Gln
NP_001177317.2:p.Arg422Gln
NP_001361726.1:p.Arg430Gln
NP_001361727.1:p.Arg422Gln
NP_005467.1:p.Arg481Gln
LRG_1197t1:c.1535G>A
LRG_1197t2:c.1442G>A
LRG_1197:g.59077G>A
LRG_1197p1:p.Arg512Gln
LRG_1197p2:p.Arg481Gln
NC_000009.11:g.36222965C>T
NM_001128227.2:c.1535G>A

Protein change:

R371Q

Links:

dbSNP: rs138357804

NCBI 1000 Genomes Browser:

rs138357804

Molecular consequence:

NM_001190383.3:c.1411+405G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001128227.3:c.1535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190384.3:c.1112G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190388.2:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374797.1:c.1289G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374798.1:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005476.7:c.1442G>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

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000632646	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000632646

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000632646.5

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 512 of the GNE protein (p.Arg512Gln). This variant is present in population databases (rs138357804, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 451929). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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

ClinVar

Relating variation to medicine