Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005460.4(SNCAIP):āc.1298A>Gā(p.Glu433Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,508 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. 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.1298A>G (p.E433G) alteration is located in exon 7 (coding exon 6) of the SNCAIP gene. This alteration results from a A to G substitution at nucleotide position 1298, causing the glutamic acid (E) at amino acid position 433 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -