ClinVar Miner

Submissions for variant NM_000027.4(AGA):c.940+1G>T

gnomAD frequency: 0.00001  dbSNP: rs386833437
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000000251 SCV000220824 likely pathogenic Aspartylglucosaminuria 2014-10-21 criteria provided, single submitter literature only
Invitae RCV000000251 SCV003525619 pathogenic Aspartylglucosaminuria 2023-10-22 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 of the AGA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs386833437, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with aspartylglucosaminuria (PMID: 1722323, 1879549). ClinVar contains an entry for this variant (Variation ID: 227). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects AGA function (PMID: 1879549). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in skipping of exon 8 and introduces a new termination codon (PMID: 1879549). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000251 SCV000020395 pathogenic Aspartylglucosaminuria 1991-12-15 no assertion criteria provided literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000000251 SCV000081797 probable-pathogenic Aspartylglucosaminuria no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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