ClinVar Miner

Submissions for variant NM_152703.5(SAMD9L):c.683G>A (p.Cys228Tyr)

dbSNP: rs1433514195
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001961915 SCV002132615 uncertain significance not provided 2021-07-04 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this variant affects SAMD9L protein function (PMID: 30322869). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has been observed in individual(s) with primary myelofibrosis (PMID: 30322869). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 228 of the SAMD9L protein (p.Cys228Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine.
Neuberg Centre For Genomic Medicine, NCGM RCV003448423 SCV004176620 uncertain significance Ataxia-pancytopenia syndrome 2023-02-14 criteria provided, single submitter clinical testing The missense c.683G>A (p.Cys228Tyr) variant in SAMD9L gene has been has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Cys228Tyr variant has allele frequency 0.0004% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Cys228Tyr in SAMD9L is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Cys at position 228 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Neuberg Centre For Genomic Medicine, NCGM RCV004577003 SCV005060972 uncertain significance Spinocerebellar ataxia 49 criteria provided, single submitter clinical testing The missense c.683G>A (p.Cys228Tyr) variant in the SAMD9L gene has been reported previously in an individual affected with myelodysplastic syndromes (Nagata et al., 2018). The p.Cys228Tyr variant has an allele frequency of 0.0004% in gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Cysteine at position 228 is changed to a Tyrosine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Cys228Tyr in SAMD9L is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).

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