Submissions for variant NM_020366.4(RPGRIP1):c.953C>G (p.Ala318Gly)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002471935	SCV002767591	uncertain significance	Cone-rod dystrophy 13	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_020366.3(RPGRIP1):c.953C>G in exon 8 of 24 of the RPGRIP1 gene. This substitution is predicted to create a minor amino acid change from alanine to glycine at position 318 of the protein, NP_065099.3(RPGRIP1):p.(Ala318Gly). The alanine at this position has low conservation (100 vertebrates, UCSC), and is located within the SMC_prok_B domain and a coiled_coil motif. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is not present in the gnomAD population database. Two alternative residue changes at the same location to a serine and a valine have been reported in the gnomAD database at a frequency of 0.0008% and 0.001%, respectively. The variant has not been previously reported in clinical cases. A different variant in the same codon resulting in a change to valine has been reported in a patient with primary open-angle glaucoma without clear evidence for pathogenicity described (Fernández-Martínez, L. et al. (2011)). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.