ClinVar Miner

Submissions for variant NM_003801.4(GPAA1):c.1165-1C>T

gnomAD frequency: 0.00003  dbSNP: rs187027021
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001901060 SCV002164772 likely pathogenic not provided 2024-05-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 of the GPAA1 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 GPAA1 are known to be pathogenic (PMID: 29100095). This variant is present in population databases (rs187027021, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with GPAA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1394986). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. 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.
3billion, Medical Genetics RCV002051976 SCV002318826 likely pathogenic Glycosylphosphatidylinositol biosynthesis defect 15 2022-03-22 criteria provided, single submitter clinical testing Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency:0.0000867). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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