ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.135C>A (p.Ser45Arg) (rs375493957)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671583 SCV000796571 uncertain significance Metachromatic leukodystrophy 2017-12-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780861 SCV000918480 uncertain significance not specified 2017-11-22 criteria provided, single submitter clinical testing Variant summary: The ARSA c.135C>A (p.Ser45Arg) variant located in the Sulfatase, N-terminal domain (InterPro) involves the alteration of a non-conserved nucleotide and 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO and Mutation Taster not captured due to low reliability index and p-value, respectively). This variant was found in 1/160064 control chromosomes (gnomAD) at a frequency of 0.0000062, which does not exceed the estimated maximal expected allele frequency of a pathogenic ARSA variant (0.0027951). A publication, Rafi_2003, reports the variant in a compound heterozygote 42 y/o pt, who also carried the Pd allele in cis with the variant of interest. The pt presented with mainly psychiatric issues at the age of 42 y/o and also had an affected sibling (although not genotyped). The variant of interest has not, to our knowledge, been reported by clinical diagnostic laboratories. Taken together, this variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

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