Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005460.4(SNCAIP):āc.1358T>Cā(p.Val453Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000083 in 1,613,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
SNCAIP (HGNC:11139): (synuclein alpha interacting protein) This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.1358T>C (p.V453A) alteration is located in exon 7 (coding exon 6) of the SNCAIP gene. This alteration results from a T to C substitution at nucleotide position 1358, causing the valine (V) at amino acid position 453 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -