Submissions for variant NM_000090.4(COL3A1):c.3824-14T>G

gnomAD frequency: 0.00001  dbSNP: rs762561768

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413885	SCV000492274	uncertain significance	not specified	2016-12-02	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the COL3A1 gene. The c.3824-14 T>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Several in silico splice prediction algorithms predict that this variant may destroy or damage the canonical splice acceptor site in intron 42 and may cause abnormal gene splicing. This variant may to lead to either 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. Other splice site variants in the COL3A1 gene have been reported in HGMD in association with EDS, type IV (Stenson et al., 2014). The c.3824-14 T>G variant was not observed with any significant frequency in the Exome Aggregation Consortium.
All of Us Research Program, National Institutes of Health	RCV003995923	SCV004833660	uncertain significance	Ehlers-Danlos syndrome, type 4	2023-05-04	criteria provided, single submitter	clinical testing	This variant causes a T to G nucleotide substitution at the -14 position of intron 48 of the COL3A1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 1/251172 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.