ClinVar Miner

Submissions for variant NM_000375.3(UROS):c.63+1G>A

gnomAD frequency: 0.00006  dbSNP: rs373864821
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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 RCV001851636 SCV002234736 pathogenic not provided 2021-07-21 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the UROS gene. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs373864821, ExAC 0.01%). This variant has been observed in individual(s) with congenital erythropoietic porphyria (PMID: 7860775, 11254675). ClinVar contains an entry for this variant (Variation ID: 3767). Studies have shown that this variant is associated with skipping of exon 2 and is expected to result in the loss of the initiator methionine (PMID: 7860775). This variant disrupts the p.Val3 amino acid residue in UROS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9188670, 23626549, 19099412, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003407268 SCV004115651 likely pathogenic UROS-related disorder 2023-06-05 criteria provided, single submitter clinical testing The UROS c.63+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in an individual with Porphyria, erythropoietic (IVS2+1 in Xu et al. 1995. PubMed ID: 7860775; Solis et al. 2001. PubMed ID: 11254675). This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-127505005-C-T). Variants that disrupt the consensus splice donor site in UROS are expected to be pathogenic. This variant is interpreted as likely pathogenic.
OMIM RCV000003965 SCV000024130 pathogenic Cutaneous porphyria 2001-03-01 no assertion criteria provided literature only

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