Submissions for variant NM_020680.4(SCYL1):c.526A>T (p.Lys176Ter)

gnomAD frequency: 0.00003  dbSNP: rs535912271

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853313	SCV000996160	pathogenic	Acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome	2018-06-27	criteria provided, single submitter	clinical testing	This nonsense variant found in exon 4 of 18 is predicted to result in loss of normal protein function. Loss of function variants are an established mechanism for disease in SCYL1. This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.526A>T (p.Lys176Ter) variant is predicted by multiple in silico tools to have a deleterious effect on protein function. This variant was detected in trans with a pathogenic variant. Based on the available evidence, the c.526A>T (p.Lys176Ter) variant is classified as pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003424376	SCV004107051	likely pathogenic	SCYL1-related condition	2022-10-02	criteria provided, single submitter	clinical testing	The SCYL1 c.526A>T variant is predicted to result in premature protein termination (p.Lys176*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in SCYL1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.