ClinVar Miner

Submissions for variant NM_016955.4(SEPSECS):c.548-1G>A

gnomAD frequency: 0.00014  dbSNP: rs200041461
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498347 SCV000590091 uncertain significance not provided 2017-06-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SEPSECS gene. The c.548-1 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.548-1 G>A variant is observed in 11/6578 (0.2%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.548-1 G>A splice site variant destroys the canonical splice acceptor site in intron 4. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000498347 SCV002315729 likely pathogenic not provided 2022-06-09 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects an acceptor splice site in intron 4 of the SEPSECS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SEPSECS are known to be pathogenic (PMID: 25558065, 25590979, 26115735). This variant is present in population databases (rs200041461, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SEPSECS-related conditions. ClinVar contains an entry for this variant (Variation ID: 432373). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV001834608 SCV002082962 uncertain significance Pontocerebellar hypoplasia type 2D 2020-10-01 no assertion criteria provided clinical testing

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