ClinVar Miner

Submissions for variant NM_015474.3(SAMHD1):c.625G>A (p.Gly209Ser) (rs121434516)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000004281 SCV000147936 pathogenic Aicardi Goutieres syndrome 5 2014-03-13 no assertion criteria provided literature only
Invitae RCV000004281 SCV000956910 uncertain significance Aicardi Goutieres syndrome 5 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 209 of the SAMHD1 protein (p.Gly209Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 5 of the SAMHD1 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs121434516, ExAC 0.001%). This variant has been observed to segregate with Aicardi-Goutières syndrome in a family (PMID: 19525956). ClinVar contains an entry for this variant (Variation ID: 4066). This variant has been reported to have conflicting or insufficient data to determine the effect on SAMHD1 protein function (PMID: 22461318, 24035396, 28229507). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
OMIM RCV000004281 SCV000024447 pathogenic Aicardi Goutieres syndrome 5 2009-07-01 no assertion criteria provided literature only

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