ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.587C>A (p.Ser196Tyr)

dbSNP: rs865899394
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000672941 SCV005442776 uncertain significance Phenylketonuria 2024-03-08 reviewed by expert panel curation The c.587C>A (p.Ser196Tyr) variant in PAH has been reported in one individual with mild hyperphenylalanemia, without exclusion of BH4 deficiency (PMID: 23792259). In this individual, c.587C>A occurred de novo on the paternal allele, with confirmation of paternity. c.842+3G>C was present on the maternal allele (classified as likely pathogenic by PAH VCEP, Variation ID: 102871). In-vitro studies show 21% enzyme activity (PMID: 27620137). This variant is present below the 0.0002 allele frequency threshold for PAH in population databases. Multiple lines of computational evidence yield conflicting predictions regarding the effect of this variant (REVEL=0.542). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM3, PP4, PM2_supporting, PS3_supporting.
Counsyl RCV000672941 SCV000798098 uncertain significance Phenylketonuria 2018-02-28 criteria provided, single submitter clinical testing

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