ClinVar Miner

Submissions for variant NM_004544.4(NDUFA10):c.1A>G (p.Met1Val)

gnomAD frequency: 0.00001  dbSNP: rs387906872
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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 RCV000023345 SCV002570776 likely pathogenic Mitochondrial complex 1 deficiency, nuclear type 22 2022-07-19 criteria provided, single submitter clinical testing Variant summary: NDUFA10 c.1A>G (p.Met1?, aka p.Met1Val) alters the initiation codon and is predicted to result either in absence of the protein or truncation/extension of the encoded protein due to translation initiation at a downstream/upstream codon. No upstream in-frame ATG triplets were found that could generate an N-terminally extended protein product, and although a downstream in-frame ATG triplet was found, (i.e. Met40 in Exon 2), the utilization of Met40 as a start codon would result in an N-terminally truncated protein product, with the loss of the mitochondrial targeting signal (i.e. the 35 N-terminal amino acids; see Dang_2020). The variant allele was found at a frequency of 2.9e-05 in 103762 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.1A>G, has been reported in the literature in a compound heterozygous individual affected with Mitochondrial Complex 1 Deficiency, Nuclear Type 22 (Hoefs_2011), and the authors of this study described a marked decrease of complex I activity in patient derived fibroblasts and muscle tissue, together with a strongly decreased NDUFA10 protein level on Western blot analysis. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000023345 SCV000044636 pathogenic Mitochondrial complex 1 deficiency, nuclear type 22 2011-03-01 no assertion criteria provided literature only

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