ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.879C>T (p.Gly293=)

gnomAD frequency: 0.00004  dbSNP: rs769683236
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001415649 SCV001617811 likely benign Familial thoracic aortic aneurysm and aortic dissection 2023-11-05 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001415649 SCV001734292 likely benign Familial thoracic aortic aneurysm and aortic dissection 2020-07-13 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279574 SCV002566109 uncertain significance Ehlers-Danlos syndrome 2019-05-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000866494 SCV001552083 uncertain significance not provided no assertion criteria provided clinical testing The SMAD3 p.Gly249Gly variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs769683236) and in control databases in 19 of 282784 chromosomes at a frequency of 0.000067 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 7228 chromosomes (freq: 0.000138), European (non-Finnish) in 16 of 129092 chromosomes (freq: 0.000124), South Asian in 1 of 30616 chromosomes (freq: 0.000033) and Latino in 1 of 35440 chromosomes (freq: 0.000028); it was not observed in the African, Ashkenazi Jewish, East Asian, and European (Finnish) populations. The p.Gly249Gly variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence however 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, and NNSPLICE) predict a greater than 10% difference in splicing and the creation of a new 5' splice site. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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