ClinVar Miner

Submissions for variant NM_001171613.2(PREPL):c.967A>G (p.Ile323Val)

gnomAD frequency: 0.00051  dbSNP: rs143785426
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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 RCV001484643 SCV001689063 likely benign Myasthenic syndrome, congenital, 22 2024-01-12 criteria provided, single submitter clinical testing
GeneDx RCV001357101 SCV001998832 uncertain significance not provided 2020-01-23 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357101 SCV001552452 uncertain significance not provided no assertion criteria provided clinical testing The PREPL p.I323V variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs143785426) and in control databases in 66 of 282772 chromosomes at a frequency of 0.0002334, and was observed at the highest frequency in the African population in 55 of 24968 chromosomes (freq: 0.002203) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.I323 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome, Splice AI genome) predict a deleterious effect on splicing. However, this information is not predictive enough to assume pathogenicity. 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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