ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.870T>C (p.His290=)

gnomAD frequency: 0.00002  dbSNP: rs751203209
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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 RCV001279863 SCV004015319 uncertain significance Phenylketonuria 2023-07-23 reviewed by expert panel curation The NM_000277.3:c.870T>C variant in PAH is a synonymous (silent) variant (p.His290=) that is not predicted to impact splicing. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001694 (6/35412 alleles) in the Latino/Admixed American population, which is lower than the ClinGen PAH VCEP’s threshold for PM2_Supporting (<0.0002), meeting this criterion (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 991620, 1 star review status) with one submitter classifying the variant as a variant of uncertain significance and one submitter classifying the variant as likely benign. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH Variant Curation Expert Panel (Specifications Version 2.0): PM2_Supporting.
Invitae RCV001279863 SCV001642054 likely benign Phenylketonuria 2024-01-13 criteria provided, single submitter clinical testing
Natera, Inc. RCV001279863 SCV001466996 uncertain significance Phenylketonuria 2020-04-17 no assertion criteria provided clinical testing

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