ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.471G>A (p.Ser157=) (rs760318745)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701864 SCV000830685 uncertain significance Neuronal ceroid lipofuscinosis 2018-04-16 criteria provided, single submitter clinical testing This sequence change affects codon 157 of the CTSD mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CTSD protein. This variant also falls at the last nucleotide of exon 4 of the CTSD coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs760318745, ExAC 0.01%). This variant has not been reported in the literature in individuals with CTSD-related disease. Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000720420 SCV000851297 uncertain significance Seizures 2017-01-18 criteria provided, single submitter clinical testing The c.471G>A variant (also known as p.S157S), located in coding exon 4 of the CTSD gene, results from a G to A substitution at nucleotide position 471. This nucleotide substitution does not change the amino acid at codon 157. However, this change occurs in the last base pair of coding exon 4, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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