Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001061485 | SCV001226229 | pathogenic | Multiple sulfatase deficiency | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the SUMF1 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 SUMF1 are known to be pathogenic (PMID: 12757705, 12757706, 25885655). This variant is present in population databases (rs143616931, gnomAD 0.02%). Disruption of this splice site has been observed in individual(s) with atypical multiple sulfatase deficiency (PMID: 26825355). ClinVar contains an entry for this variant (Variation ID: 856092). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001061485 | SCV001362111 | likely pathogenic | Multiple sulfatase deficiency | 2021-08-06 | criteria provided, single submitter | clinical testing | Variant summary: SUMF1 c.602+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251100 control chromosomes. c.602+1G>A has been reported in the literature in compound heterozygosity with another SUMF1 variant in at-least one individual affected with atypical Multiple Sulfatase Deficiency (example, Miskin_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two 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 likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Natera, |
RCV001061485 | SCV001460171 | likely pathogenic | Multiple sulfatase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |