ClinVar Miner

Submissions for variant NM_005360.5(MAF):c.206C>G (p.Pro69Arg)

dbSNP: rs727502768
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413144 SCV000491194 likely pathogenic not provided 2016-09-22 criteria provided, single submitter clinical testing The P69R likely pathogenic variant has been previously reported as an assumed de novo variant identified in an individual with cataracts, blindness, sensorineural hearing loss, seizures, brachycephaly, facial dysmorphism, short stature, intellectual disability and autistic features (Gripp et al., 1996; Niceta et al., 2015). Functional and expression studies have shown P69R exhibits less activity than wild type and impairs phosphorylation of the MAF protein by altering a Proline residue adjacent to the phosphorylation site (Niceta et al., 2015). The P69R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with MAF-related disorders (Stenson et al., 2014). Therefore, the P69R variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Reparto di Fisiopatologia delle Malattie Genetiche, Dipartimento di Ematologia, Oncologia; Istituto Superiore di Sanità RCV000149908 SCV000196759 pathogenic Ayme-Gripp syndrome no assertion criteria provided not provided Converted during submission to Pathogenic.
OMIM RCV000149908 SCV000223827 pathogenic Ayme-Gripp syndrome 2015-05-07 no assertion criteria provided literature only

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