ClinVar Miner

Submissions for variant NM_033109.5(PNPT1):c.1619A>G (p.Asn540Ser)

gnomAD frequency: 0.00010  dbSNP: rs202190573
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Hereditary Hearing Loss Research Unit, University of Madras RCV001249184 SCV001366118 pathogenic Autosomal recessive nonsyndromic hearing loss 70 criteria provided, single submitter case-control
Invitae RCV002069318 SCV002392082 likely benign not provided 2024-01-21 criteria provided, single submitter clinical testing
GeneDx RCV002069318 SCV004036944 uncertain significance not provided 2023-09-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in the compound heterozygous state with a second PNPT1 variant in an individual with hearing loss (Vanniya et al., 2022); This variant is associated with the following publications: (PMID: 34374074)
Neuberg Centre For Genomic Medicine, NCGM RCV003339565 SCV004048004 uncertain significance Combined oxidative phosphorylation defect type 13 criteria provided, single submitter clinical testing The missense variant c.1619A>G (p.Asn540Ser) in PNPT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Pathogenic. The p.Asn540Ser variant is reported with allele frequency of 0.02% in gnomAD exomes and novel in gnomAD Exomes and 1000 Genomes. The amino acid Asn at position 540 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Asn540Ser in PNPT1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. In the absence of another reportable variant the molecular diagnosis is not confirmed.

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