ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.45+3A>G

dbSNP: rs1554340088
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497841 SCV000590219 uncertain significance not provided 2018-01-17 criteria provided, single submitter clinical testing The c.45+3 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.45+3 A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.45+3 A>G damages or destroys the natural splice donor site for inton 1 and leads to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002463685 SCV002605183 uncertain significance Maturity onset diabetes mellitus in young criteria provided, single submitter research Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1554340088 in MODY, yet.
Labcorp Genetics (formerly Invitae), Labcorp RCV000497841 SCV005762149 uncertain significance not provided 2024-07-30 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the GCK gene. It does not directly change the encoded amino acid sequence of the GCK protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of GCK-related conditions (PMID: 36257325). ClinVar contains an entry for this variant (Variation ID: 432488). 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.

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