ClinVar Miner

Submissions for variant NM_015909.4(NBAS):c.1361C>G (p.Pro454Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003070883 SCV003445703 benign not provided 2023-09-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003317642 SCV004021133 uncertain significance not specified 2023-06-19 criteria provided, single submitter clinical testing Variant summary: NBAS c.1361C>G (p.Pro454Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 249556 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in NBAS causing Liver Failure Acute Infantile, Type 2 (6.4e-05 vs 0.0011), allowing no conclusion about variant significance. c.1361C>G has been reported in the literature in compound heterozygous individuals with features of NBAS-related conditions without indication of acute liver failure and without strong evidence of causality (Li_2020, Bi_2022). These reports do not provide unequivocal conclusions about association of the variant with Liver Failure Acute Infantile, Type 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32812336, 35902954). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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