Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001242792.2(SNAP91):c.2017T>C(p.Phe673Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
SNAP91 (HGNC:14986): (synaptosome associated protein 91) Predicted to enable several functions, including SNARE binding activity; clathrin binding activity; and phosphatidylinositol binding activity. Acts upstream of or within regulation of clathrin-dependent endocytosis. Predicted to be located in several cellular components, including postsynaptic density; presynaptic endosome; and presynaptic membrane. Predicted to be extrinsic component of endosome membrane. Predicted to be active in several cellular components, including Schaffer collateral - CA1 synapse; cytoplasmic vesicle; and parallel fiber to Purkinje cell synapse. Predicted to be extrinsic component of presynaptic endocytic zone membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.33989227).
Uncertain significance, criteria provided, single submitter
clinical testing
Ambry Genetics
Nov 17, 2023
The c.2017T>C (p.F673L) alteration is located in exon 23 (coding exon 22) of the SNAP91 gene. This alteration results from a T to C substitution at nucleotide position 2017, causing the phenylalanine (F) at amino acid position 673 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Gain of glycosylation at S676 (P = 0.0902);Gain of glycosylation at S676 (P = 0.0902);Gain of glycosylation at S676 (P = 0.0902);Gain of glycosylation at S676 (P = 0.0902);Gain of glycosylation at S676 (P = 0.0902);.;.;.;.;