ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.243C>T (p.Gly81=) (rs6151410)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000262492 SCV000331612 benign not specified 2016-01-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000276455 SCV000439442 benign Metachromatic leukodystrophy 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000276455 SCV000627140 benign Metachromatic leukodystrophy 2020-12-08 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000276455 SCV000677129 benign Metachromatic leukodystrophy 2017-06-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000262492 SCV001360434 benign not specified 2019-04-01 criteria provided, single submitter clinical testing Variant summary: ARSA c.243C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant alterations at the canonical splice site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0076 in 259806 control chromosomes, predominantly at a frequency of 0.079 within the African subpopulation in the gnomAD database, including 65 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in ARSA causing Metachromatic Leukodystrophy phenotype (0.0028), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.243C>T in individuals affected with Metachromatic Leukodystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (X4) /likely benign (X1). Based on the evidence outlined above, the variant was classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000675753 SCV000801473 benign not provided 2017-05-16 no assertion criteria provided clinical testing
Natera, Inc. RCV000276455 SCV001452359 benign Metachromatic leukodystrophy 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.