ClinVar Miner

Submissions for variant NM_003896.4(ST3GAL5):c.82+1G>C

gnomAD frequency: 0.00001  dbSNP: rs878854615
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000229539 SCV000288016 likely pathogenic GM3 synthase deficiency 2023-09-10 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 239583). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the ST3GAL5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ST3GAL5 are known to be pathogenic (PMID: 15502825, 22990144, 27232954).
Illumina Laboratory Services, Illumina RCV000229539 SCV000914945 uncertain significance GM3 synthase deficiency 2018-03-16 criteria provided, single submitter clinical testing The ST3GAL5 c.82+1G>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance, but suspicious for pathogenicity for Amish infantile epilepsy syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Baylor Genetics RCV000229539 SCV001520496 likely pathogenic GM3 synthase deficiency 2019-11-15 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV004020809 SCV004958474 uncertain significance Inborn genetic diseases 2023-11-01 criteria provided, single submitter clinical testing The c.82+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 1 of the ST3GAL5 gene. This region of the ST3GAL5 gene is excluded from other biologically relevant ST3GAL5 transcripts. This allele was reported in one heterozygous individual in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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