ClinVar Miner

Submissions for variant NM_006118.4(HAX1):c.46C>T (p.Pro16Ser)

gnomAD frequency: 0.00001  dbSNP: rs763746492
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000702882 SCV000831754 uncertain significance Kostmann syndrome 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 16 of the HAX1 protein (p.Pro16Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs763746492, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000702882 SCV003920024 uncertain significance Kostmann syndrome 2022-10-05 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.02% [7/34568]; https://gnomad.broadinstitute.org/variant/1-154245245-C-T?dataset=gnomad_r2_1), and in ClinVar (Variation ID: 579564). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004972889 SCV005596170 uncertain significance Inborn genetic diseases 2024-11-26 criteria provided, single submitter clinical testing The p.P16S variant (also known as c.46C>T), located in coding exon 1 of the HAX1 gene, results from a C to T substitution at nucleotide position 46. The proline at codon 16 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Natera, Inc. RCV000702882 SCV002085814 uncertain significance Kostmann syndrome 2019-10-28 no assertion criteria provided clinical testing

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