ClinVar

Description

The NPHS1 p.Pro264Gln variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs34982899). The variant was identified in control databases in 43 of 280518 chromosomes at a frequency of 0.000153 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 40 of 127584 chromosomes (freq: 0.000314), Other in 1 of 7176 chromosomes (freq: 0.000139), African in 1 of 24694 chromosomes (freq: 0.000041) and Latino in 1 of 35350 chromosomes (freq: 0.000028); it was not observed in the Ashkenazi Jewish, East Asian, European (Finnish) and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Pro264 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, 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. This variant is classified as a variant of uncertain significance.