Submissions for variant NM_015909.4(NBAS):c.4520del (p.Leu1507fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002470102	SCV002766390	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2022-11-09	criteria provided, single submitter	clinical testing	Variant summary: NBAS c.4520delT (p.Leu1507CysfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory and in ClinVar. The variant allele was found at a frequency of 4e-06 in 251028 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4520delT in individuals affected with Liver Failure Acute Infantile, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002569373	SCV002978573	pathogenic	not provided	2022-06-14	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.003%). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NBAS-related conditions. This sequence change creates a premature translational stop signal (p.Leu1507Cysfs*2) in the NBAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453).