ClinVar Miner

Submissions for variant NM_002778.4(PSAP):c.578A>G (p.Asp193Gly)

gnomAD frequency: 0.00036  dbSNP: rs138636858
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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 RCV002069482 SCV002461188 likely benign Sphingolipid activator protein 1 deficiency 2024-12-16 criteria provided, single submitter clinical testing
Natera, Inc. RCV001280277 SCV001467442 likely benign Metachromatic leukodystrophy 2020-08-28 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354629 SCV001549290 uncertain significance not provided no assertion criteria provided clinical testing The PSAP p.D193G variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs138636858), LOVD 3.0 (classified as likely benign), and identified in control databases in 108 of 282888 chromosomes (1 homozygous) at a frequency of 0.0003818 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 35 of 30616 chromosomes (freq: 0.001143), Other in 4 of 7226 chromosomes (freq: 0.000554), European (non-Finnish) in 62 of 129188 chromosomes (freq: 0.00048), African in 5 of 24970 chromosomes (freq: 0.0002) and Latino in 2 of 35440 chromosomes (freq: 0.000056), but was not observed in the Ashkenazi Jewish, East Asian, or European (Finnish) populations. The p.Asp193 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and three of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing, i.e. the creation of a new 5’ splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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