Submissions for variant NM_014956.5(CEP164):c.3332G>A (p.Arg1111His)

gnomAD frequency: 0.00110  dbSNP: rs61740738

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000950908	SCV001097251	likely benign	Nephronophthisis 15	2025-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002546023	SCV003538408	uncertain significance	Inborn genetic diseases	2022-10-03	criteria provided, single submitter	clinical testing	The c.3332G>A (p.R1111H) alteration is located in exon 27 (coding exon 25) of the CEP164 gene. This alteration results from a G to A substitution at nucleotide position 3332, causing the arginine (R) at amino acid position 1111 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV004588401	SCV005078511	uncertain significance	not provided	2023-07-17	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Breakthrough Genomics, Breakthrough Genomics	RCV004588401	SCV005218603	likely benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV003151232	SCV003839345	uncertain significance	not specified	2022-11-21	no assertion criteria provided	clinical testing	DNA sequence analysis of the CEP164 gene demonstrated a sequence change, c.3332G>A, in exon 27 that results in an amino acid change, p.Arg1111His. This sequence change has been described in the gnomAD database with a frequency of 0.43% in the African/African American subpopulation (dbSNP rs61740738). The p.Arg1111His change affects a moderately conserved amino acid residue located in a domain of the CEP164 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg1111His substitution. This sequence change does not appear to have been previously described in individuals with CEP164-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Arg1111His change remains unknown at this time. Biallelic pathogenic variants in CEP164 are associated with nephronophthisis, an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence [MIM Number 614845].
PreventionGenetics, part of Exact Sciences	RCV003903214	SCV004721971	likely benign	CEP164-related disorder	2020-04-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).