ClinVar Miner

Submissions for variant NM_000538.4(RFXAP):c.127C>T (p.Gln43Ter)

gnomAD frequency: 0.00002  dbSNP: rs1313207845
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000686231 SCV000813740 pathogenic MHC class II deficiency 2024-04-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln43*) in the RFXAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RFXAP are known to be pathogenic (PMID: 9118943, 22390233). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RFXAP-related conditions. ClinVar contains an entry for this variant (Variation ID: 566425). For these reasons, this variant has been classified as Pathogenic.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV002282326 SCV002009088 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000686231 SCV002570640 likely pathogenic MHC class II deficiency 2022-07-14 criteria provided, single submitter clinical testing Variant summary: RFXAP c.127C>T (p.Gln43X) 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. The variant allele was found at a frequency of 1.4e-05 in 147392 control chromosomes. To our knowledge, no occurrence of c.127C>T in individuals affected with Bare Lymphocyte Syndrome 2 - RFXAP Related and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV002282326 SCV002571548 pathogenic not provided 2022-09-04 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614)
3billion RCV000686231 SCV003841703 pathogenic MHC class II deficiency 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000566425 / PMID: 31589614). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV005010678 SCV005634008 likely pathogenic MHC class II deficiency 4 2024-06-11 criteria provided, single submitter clinical testing

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