Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV005208320 | SCV005849310 | likely pathogenic | Geroderma osteodysplastica | criteria provided, single submitter | clinical testing | The start lost c.1A>G (p.Met1?) variant in GORAB The start lost c.1A>G (p.Met1?) variant in GORAB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with allele frequency of 0.003% in gnomAD Genomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid at this position on GORAB is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The p.Met1? variant is predicted to disrupt the initiation codon, and thus potentially may interfere with protein expression. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with allele frequency of 0.003% in gnomAD Genomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidence (Polyphen - Probably Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The reference amino acid at this position on GORAB is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The p.Met1? variant is predicted to disrupt the initiation codon, and thus potentially may interfere with protein expression. However, additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic. |