NM_005476.7(GNE):c.1411G>A (p.Gly471Ser) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 2023
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:: RCV001908556.5

Allele description [Variation Report for NM_005476.7(GNE):c.1411G>A (p.Gly471Ser)]

NM_005476.7(GNE):c.1411G>A (p.Gly471Ser)

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.1411G>A (p.Gly471Ser)

HGVS:

NC_000009.12:g.36223373C>T
NG_008246.1:g.58672G>A
NM_001128227.3:c.1504G>A
NM_001190383.3:c.1411G>A
NM_001190384.3:c.1081G>A
NM_001190388.2:c.1234G>A
NM_001374797.1:c.1258G>A
NM_001374798.1:c.1234G>A
NM_005476.7:c.1411G>AMANE SELECT
NP_001121699.1:p.Gly502Ser
NP_001177312.1:p.Gly471Arg
NP_001177313.1:p.Gly361Ser
NP_001177317.2:p.Gly412Ser
NP_001361726.1:p.Gly420Ser
NP_001361727.1:p.Gly412Ser
NP_005467.1:p.Gly471Ser
LRG_1197t1:c.1504G>A
LRG_1197t2:c.1411G>A
LRG_1197:g.58672G>A
LRG_1197p1:p.Gly502Ser
LRG_1197p2:p.Gly471Ser
NC_000009.11:g.36223370C>T

Protein change:

G361S

Links:

dbSNP: rs2133023974

NCBI 1000 Genomes Browser:

rs2133023974

Molecular consequence:

NM_001128227.3:c.1504G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190383.3:c.1411G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190384.3:c.1081G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190388.2:c.1234G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374797.1:c.1258G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374798.1:c.1234G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005476.7:c.1411G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002163149	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 22, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002163149

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 22, 2023)

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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002163149.3

#	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 glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 502 of the GNE protein (p.Gly502Ser). This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). 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: 1389211). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Mar 5, 2024

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