ClinVar Miner

Submissions for variant NM_018161.5(NADSYN1):c.524G>A (p.Cys175Tyr)

dbSNP: rs764123669
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002273165 SCV002557844 likely pathogenic Vertebral, cardiac, renal, and limb defects syndrome 3 2022-06-24 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with vertebral, cardiac, renal, and limb defects syndrome 3 (MIM#618845). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from cysteine to tyrosine. (I) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional carbon-nitrogen hydrolase domain. This domain, and specifically the critical active site Cys175 residue, has been shown to be important for glutamine dependant NAD synthetase activity (PMIDs: 12547821, 12771147). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific phenotype match for this individual. (SP) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Embryology Laboratory, Victor Chang Cardiac Research Institute RCV002273165 SCV004025918 pathogenic Vertebral, cardiac, renal, and limb defects syndrome 3 2023-05-10 criteria provided, single submitter research

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