Submissions for variant NM_005902.4(SMAD3):c.607+4A>C

gnomAD frequency: 0.00005  dbSNP: rs1465673227

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000827038	SCV000968650	likely benign	not provided	2018-05-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
All of Us Research Program, National Institutes of Health	RCV004002872	SCV004821655	uncertain significance	Aneurysm-osteoarthritis syndrome	2024-07-29	criteria provided, single submitter	clinical testing	This variant causes an A to C nucleotide substitution at the +4 position of intron 4 of the SMAD3 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SMAD3-related disorders in the literature. This variant has been identified in 3/236272 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.