Submissions for variant NM_152703.5(SAMD9L):c.4148C>T (p.Ser1383Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004764883	SCV005374810	uncertain significance	Ataxia-pancytopenia syndrome		criteria provided, single submitter	clinical testing	The missense variant c.4148C>T (p.Ser1383Phe) in the SAMD9L gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is absent in the gnomAD Exomes. The amino acid Serine at position 1383 is changed to a Phenylalanine changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence (Polyphen, SIFT and MutationTaster) predicts conflicting evidence on protein structure and function for this variant. The amino acid change p.Ser1383Phe in SAMD9L is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Ambry Genetics	RCV004968632	SCV005497623	likely benign	Inborn genetic diseases	2024-10-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.