ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.441+20G>A

gnomAD frequency: 0.00229  dbSNP: rs111842675
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002124547 SCV002442785 benign Phenylketonuria 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282695 SCV002570566 likely benign not specified 2022-07-05 criteria provided, single submitter clinical testing Variant summary: PAH c.441+20G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00043 in 251480 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in PAH causing Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (0.00043 vs 0.0079), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.441+20G>A in individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign.
Breakthrough Genomics, Breakthrough Genomics RCV004707784 SCV005235506 benign not provided criteria provided, single submitter not provided

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