ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1315+5G>C

dbSNP: rs1874533541
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001093512 SCV001250544 likely pathogenic Phenylketonuria 2024-09-06 reviewed by expert panel curation The c.1315+5G>C variant in PAH is an intronic variant in intron 12 that is predicted by multiple splicing tools to alter splicing (PP3) and is absent from gnomAD v2.1.1 (PM2_Supporting). It has been observed in at least 2 moderate or classic PKU patients with BH4 deficiency excluded (PMID: 30747360, PMID: 33980295; PP4_moderate), including 1 case who harbored it in trans (parental genetic analysis reportedly done for all cases) with the known pathogenic variant p.Arg252Gln (ClinVar ID 102824) (PM3_Moderate). In summary, this variant meets criteria to be classified as Likely Pathogenic based on the ACMG/AMP criteria applied, as specified by the ClinGen Phenylketonuria Variant Curation Expert Panel (Specifications Version 2.0): PM2_Supporting, PM3_Moderate, PP4_Moderate, PP3_Supporting.

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