Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001353108.3(CEP63):c.1155C>A(p.Asn385Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,610,376 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N385T) has been classified as Uncertain significance.
CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
Computational evidence support a benign effect (MetaRNN=0.0047411025).
BP6
Variant 3-134549149-C-A is Benign according to our data. Variant chr3-134549149-C-A is described in ClinVar as [Benign]. Clinvar id is 128707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-134549149-C-A is described in Lovd as [Benign]. Variant chr3-134549149-C-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00685 (1043/152184) while in subpopulation AFR AF= 0.023 (953/41516). AF 95% confidence interval is 0.0217. There are 7 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
.;.;.;Gain of ubiquitination at N385 (P = 0.0109);Gain of ubiquitination at N385 (P = 0.0109);Gain of ubiquitination at N385 (P = 0.0109);Gain of ubiquitination at N385 (P = 0.0109);.;