Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007245.4(ATXN2L):c.428C>T(p.Thr143Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.428C>T (p.T143I) alteration is located in exon 4 (coding exon 4) of the ATXN2L gene. This alteration results from a C to T substitution at nucleotide position 428, causing the threonine (T) at amino acid position 143 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);Loss of ubiquitination at K140 (P = 0.0594);.;.;