Submissions for variant NM_004187.5(KDM5C):c.548A>G (p.Asn183Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003329644	SCV004036342	uncertain significance	not provided	2023-03-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Neuberg Centre For Genomic Medicine, NCGM	RCV004577037	SCV005061206	uncertain significance	Syndromic X-linked intellectual disability Claes-Jensen type		criteria provided, single submitter	clinical testing	The observed missense c.548A>G (p.Asn183Ser) variant in KDM5C gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn183Ser variant is present with an allele frequency of 0.0006% on gnomAD exomes database. This variant has not been reported to the ClinVar database. Computational evidence (SIFT - tolerated; Polyphen - benign; MutationTaster - disease causing) predicts conflicting evidence on protein structure and function for this variant. The amino acid change p.Asn183Ser in KDM5C is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 183 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).