ClinVar Miner

Submissions for variant NM_000137.4(FAH):c.47A>T (p.Asn16Ile)

dbSNP: rs121965073
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000012640 SCV004030028 likely pathogenic Tyrosinemia type I 2023-07-25 criteria provided, single submitter clinical testing Variant summary: FAH c.47A>T (p.Asn16Ile) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Fumarylacetoacetase, N-terminal (IPR015377) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251278 control chromosomes (gnomAD). c.47A>T has been reported in the literature in an individual affected with Tyrosinemia Type 1 (Phaneuf_1992). These data suggest the variant may be associated with disease. At least three publications report experimental evidence evaluating an impact on protein function, finding that the variant protein lacks enzymatic activity and shows aberrant aggregation in the insoluble fraction of cells (Phaneuf_1992, Bergeron_2001, Macias_2019). The following publications have been ascertained in the context of this evaluation (PMID: 1401056, 11278491, 31300554). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000012640 SCV000032875 pathogenic Tyrosinemia type I 1992-10-01 no assertion criteria provided literature only

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