Description
The SACS p.Asn1342Ser variant was not identified in the literature nor was it identified in Cosmic, MutDB, and LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs147099630) as "With Likely pathogenic allele". In ClinVar, there are five submissions with conflicting interpretations of pathogenicity: likely pathogenic (Lupski Lab, Baylor-Hopkins CMG,Baylor College of Medicine), benign (Invitae and EGL Genetic Diagnostics) and uncertain significance (Genetic Services Laboratory, University of Chicago). The associated conditions are: Spastic ataxia Charlevoix-Saguenay type, abnormality of brain morphology, and Spastic paraplegia. The variant was identified in control databases in 2472 of 278622 chromosomes (33 homozygous) at a frequency of 0.008872 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 440 of 10136 chromosomes (freq: 0.04341), South Asian in 924 of 29334 chromosomes (freq: 0.0315), Other in 66 of 7086 chromosomes (freq: 0.009314), European (non-Finnish) in 880 of 127810 chromosomes (freq: 0.006885), while the variant was not observed in the Latino, European (Finnish), African, and East Asian populations. The variant was also identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016). The p.Asn1342 residue is conserved in mammals but not in more distantly related organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, and BLOSUM) do not suggest a high likelihood of impact to the protein. MutationTaster predicts an impact to the protein. However, all this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
