Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000579170 | SCV000681127 | uncertain significance | not provided | 2017-11-28 | criteria provided, single submitter | clinical testing | The c.2148+6 A>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2148+6 A>T variant is observed in 17/24,000 (0.07%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016). Although in silico splice prediction models do not predict that c.2148+6 A>T affects gene splicing, 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. |
Invitae | RCV000579170 | SCV002311434 | uncertain significance | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 26 of the PNPT1 gene. It does not directly change the encoded amino acid sequence of the PNPT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs374690825, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 489141). 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. |
Prevention |
RCV004543283 | SCV004786304 | likely benign | PNPT1-related disorder | 2019-03-18 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |