ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.757G>A (p.Asp253Asn) (rs765533320)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000984203 SCV001250552 uncertain significance Phenylketonuria 2020-01-26 reviewed by expert panel curation The c.757G>A (p.Asp253Asn) variant in PAH has not been reported in the literature to our knowledge. This variant has an extremely low frequency in ExAC and gnomAD (MAF=0.00001). Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.
GeneDx RCV000484615 SCV000571414 likely pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing The D253N missense variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D253N 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 D253N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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. In summary, we interpret D253N as likely pathogenic.
Counsyl RCV000984203 SCV001132265 uncertain significance Phenylketonuria 2017-08-08 no assertion criteria provided clinical testing

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