ClinVar Miner

Submissions for variant NM_003937.3(KYNU):c.468T>A (p.Tyr156Ter) (rs758865880)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Embryology Laboratory,Victor Chang Cardiac Research Institute RCV000496184 SCV000540922 pathogenic Congenital NAD deficiency disorder 2016-12-23 criteria provided, single submitter research This variant was discovered in a North American family. The patient presented multiple congenital malformations affecting vertebrae, heart, kidney among others. This variant is a protein truncating variant and extremely rare (ExAC MAF 0.0001419). The patient is compound heterzygous for this variant and another protein truncating variant in the same KYNU gene (NM_003937.2:c.1045_1051delTTTAAGC). Her unaffected parents are heterzygous for only one variant. Enzyme assay confirmed that the protein product of this gene variant has lost enzyme activity. Mouse embryos homozygous null for Kynu presented similar phenotype as observed in the patient, and also showed reduced concentration of NAD in the embryonic tissue.
GeneDx RCV000522905 SCV000617867 likely pathogenic not provided 2017-09-22 criteria provided, single submitter clinical testing The Y156X variant in the KYNU gene identified in this individual has now been published as a possible disease-related variant associated with NAD deficiency (Shi et al., 2017). The Y156X variant has also been published in seven individuals with schizophrenia who underwent exome sequencing, however, clinical history and familial segregation information were not included, and it is unclear if these individuals harbored variants in other genes (Purcell et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies of Y156X indicate that this variant results in absent enzyme activity (Shi et al., 2017). The Y156X variant is observed in 17/65932 (0.026%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). We interpret Y156X as likely pathogenic variant.
OMIM RCV000505808 SCV000600001 pathogenic VERTEBRAL, CARDIAC, RENAL, AND LIMB DEFECTS SYNDROME 2 2017-10-30 no assertion criteria provided literature only

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