Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004818963 | SCV005438976 | uncertain significance | Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures | 2023-06-22 | criteria provided, single submitter | clinical testing | The observed missense c.3454A>Cp.Met1152Leu variant in ARFGEF1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Met1152Leu variant is absent in gnomAD Exomes. This variant has not been submitted to the ClinVar database. Multiple lines of computational evidences Polyphen - Benign, SIFT - Tolerated and MutationTaster - Disease causing predict conflicting evidence on protein structure and function for this variant. The reference amino acid change at this position on ARFGEF1 gene is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 1152 is changed to a Leu 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. |