Description
The FAM161A p.Gln385Glu variant was identified in 1/273 unrelated patients with retinitis pigmentosa (freq=0.002) and 2/270 healthy controls (freq=0.004) (Venturini_2014_PMID: 24651477). There are also no pathogenic missense variants in FAM161A reported in ClinVar. The variant was also identified in dbSNP (ID: rs139266382), LOVD 3.0 (reported as likely benign) and ClinVar (classified as a variant of uncertain significance by EGL Genetic Diagnostics and Praxis fuer Humangenetik Tuebingen). The variant was not identified in Cosmic. The variant was identified in control databases in 945 of 279988 chromosomes (5 homozygous) at a frequency of 0.003375 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: European (non-Finnish) in 785 of 127800 chromosomes (freq: 0.006142), Other in 17 of 7126 chromosomes (freq: 0.002386), European (Finnish) in 59 of 25038 chromosomes (freq: 0.002356), African in 26 of 24182 chromosomes (freq: 0.001075), South Asian in 25 of 30600 chromosomes (freq: 0.000817), Latino in 28 of 35366 chromosomes (freq: 0.000792) and Ashkenazi Jewish in 5 of 10342 chromosomes (freq: 0.000484); it was not observed in the East Asian population. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a difference in splicing. The p.Gln385 residue is not conserved in mammals and four out of five computational analyses (SIFT, AlignGVGD, BLOSUM, and MutationTaster) do not suggest a high likelihood of impact to the protein; however, 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
| # | 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 |
