ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.110G>A (p.Arg37His)

gnomAD frequency: 0.00006  dbSNP: rs866539724
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522808 SCV000619215 uncertain significance not provided 2019-06-29 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
New York Genome Center RCV001834696 SCV002548930 uncertain significance Charlevoix-Saguenay spastic ataxia 2021-09-03 criteria provided, single submitter clinical testing The c.110G>A (p.Arg37His) variant identified in the SACS gene substitutes a moderately conserved Arginine for Histidine at amino acid 37/4580 (exon 3/10). This variant is found with low frequency in gnomAD(v3.1.1)(7 heterozygotes, 0 homozygotes; allele frequency:4.60e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Tolerated (SIFT; score: 0.138) and Benign (REVEL;score:0.1159) to the function of the canonical transcript. This variant is reported as a Variant of Uncertain Significance in ClinVar (VarID:445133), and to our current knowledge has not been reported in affected individuals in the literature. The p.Arg37residue is within the ubiquitin-like domain of SACS (UniProtKB:Q9NZJ4). Given the lack of compelling evidence for its pathogenicity, the c.110G>A (p.Arg37His) variant identified in the SACS gene is reported as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002525178 SCV003294862 likely benign Spastic paraplegia 2024-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023576 SCV004944906 uncertain significance Inborn genetic diseases 2023-09-26 criteria provided, single submitter clinical testing The c.110G>A (p.R37H) alteration is located in exon 3 (coding exon 2) of the SACS gene. This alteration results from a G to A substitution at nucleotide position 110, causing the arginine (R) at amino acid position 37 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001834696 SCV002086763 uncertain significance Charlevoix-Saguenay spastic ataxia 2019-11-11 no assertion criteria provided clinical testing

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