Submissions for variant NM_152594.3(SPRED1):c.424-4A>G

dbSNP: rs1057518328

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412862	SCV000491872	uncertain significance	not specified	2016-11-14	criteria provided, single submitter	clinical testing	The c.424-4 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In-silico splice prediction models are uninformative for the variant's effect on the natural splice acceptor site of intron 4. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001861431	SCV002189358	uncertain significance	Legius syndrome	2022-09-19	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 373287). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with SPRED1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the SPRED1 gene. It does not directly change the encoded amino acid sequence of the SPRED1 protein.