Submissions for variant NM_017654.4(SAMD9):c.1058C>T (p.Thr353Met)

gnomAD frequency: 0.00034  dbSNP: rs138478808

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV001260988	SCV001438363	likely benign	MIRAGE syndrome	2020-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV001363225	SCV001559327	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV001260988	SCV002584775	uncertain significance	MIRAGE syndrome	2022-08-01	criteria provided, single submitter	clinical testing	The SAMD9 c.1058C>T (p.Thr353Met) missense change has a maximum subpopulation frequency of 0.079% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect of this variant on protein function, however in silico predictions have not been found to correlate with syndromic risk for SAMD9 variants and are thus not considered supporting evidence of a pathogenic or benign effect (PMID: 34621053). To our knowledge, this variant has not been reported in individuals with SAMD9-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.