Submissions for variant NM_005476.7(GNE):c.1281+6A>T

gnomAD frequency: 0.00006  dbSNP: rs201025841

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725111	SCV000334073	uncertain significance	not provided	2016-12-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000302070	SCV000480098	likely benign	Inclusion Body Myopathy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000356902	SCV000480099	likely benign	Sialuria	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000262109	SCV000480100	likely benign	GNE myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000554359	SCV000632642	uncertain significance	GNE myopathy; Sialuria	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change falls in intron 7 of the GNE gene. It does not directly change the encoded amino acid sequence of the GNE protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs201025841, gnomAD 0.03%). 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: 282546). 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 is not likely to affect RNA splicing. 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.
GeneDx	RCV000725111	SCV000732402	likely benign	not provided	2021-03-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000725111	SCV001371524	likely benign	not provided	2020-05-01	criteria provided, single submitter	clinical testing