ClinVar Miner

Submissions for variant NM_014254.3(RXYLT1):c.914+6T>G

gnomAD frequency: 0.00001  dbSNP: rs748809209
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492906 SCV000582515 uncertain significance not provided 2017-05-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TMEM5 gene. The c.914+6 T>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.914+6 T>G variant not observed at a significant frequency 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.914+6 T>G reduces the natural splice donor site and may and lead 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.
Invitae RCV000492906 SCV001511899 likely pathogenic not provided 2023-11-17 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the RXYLT1 gene. It does not directly change the encoded amino acid sequence of the RXYLT1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs748809209, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of congenital muscular dystrophy (PMID: 30017359). ClinVar contains an entry for this variant (Variation ID: 429848). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 5, but is expected to preserve the integrity of the reading-frame (PMID: 30017359). 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.
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University RCV000698558 SCV002574733 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 2022-06-30 criteria provided, single submitter clinical testing

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