ClinVar Miner

Submissions for variant NM_006118.4(HAX1):c.150G>T (p.Arg50Ser)

gnomAD frequency: 0.00001  dbSNP: rs762584289
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001320135 SCV001510910 uncertain significance Kostmann syndrome 2022-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 50 of the HAX1 protein (p.Arg50Ser). This variant is present in population databases (rs762584289, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HAX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1020543). 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.
Genetic Services Laboratory, University of Chicago RCV001820009 SCV002071874 uncertain significance not specified 2021-09-20 criteria provided, single submitter clinical testing DNA sequence analysis of the HAX1 gene demonstrated a sequence change, c.150G>T, in exon 2 that results in an amino acid change, p.Arg50Ser. This sequence change does not appear to have been previously described in individuals with HAX1-related disorders. This sequence change has been described in the gnomAD database with a low frequency of 0.017% in the Latino/admixed American subpopulation (dbSNP rs762584289). The p.Arg50Ser change affects a poorly conserved amino acid residue located in a domain of the HAX1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg50Ser substitution. Due to insufficient evidence and lack of functional studies, the clinical significance of the p.Arg50Ser change remains unknown at this time.
Natera, Inc. RCV001320135 SCV002085819 uncertain significance Kostmann syndrome 2020-02-13 no assertion criteria provided clinical testing

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