Submissions for variant NM_032634.4(PIGO):c.1352T>G (p.Met451Arg)

dbSNP: rs1057518632

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413195	SCV000492442	likely pathogenic	not provided	2016-12-16	criteria provided, single submitter	clinical testing	The M451R variant in the PIGO gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M451R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M451R 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 across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. As an alternate mechanism, multiple in silico algorithms predict that this sequence change might create a cryptic splice acceptor site in exon 7 which may supplant the natural acceptor site. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The M451R variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000761591	SCV000891751	uncertain significance	Hyperphosphatasia with intellectual disability syndrome 2	2018-07-12	criteria provided, single submitter	research	ACMG codes: PM2, PP3, PP5