ClinVar Miner

Submissions for variant NM_001160372.4(TRAPPC9):c.1414C>T (p.Arg472Ter)

gnomAD frequency: 0.00003  dbSNP: rs267607137
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000273297 SCV000329560 pathogenic not provided 2021-11-08 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 22549410, 30272317, 20004764, 29187737, 30853973, 30152084, 29031008, 32434006, 34737153)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000000795 SCV000965775 likely pathogenic Intellectual disability, autosomal recessive 13 2016-01-04 criteria provided, single submitter clinical testing
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax RCV000000795 SCV001749120 pathogenic Intellectual disability, autosomal recessive 13 2021-06-09 criteria provided, single submitter clinical testing The p.Arg472Ter variant in the TRAPPC9 gene has been already reported in the homozygous state in two separately consanguineous Tunisian families of three siblings with autosomal recessive microcephaly and intellectual disability (Philippe et al., 2009 and Mortreux et al.,2018). In vitro studies of the p.Arg472Ter variant revealed undetectable levels of TRAPPC9 protein in skin fibroblasts from a patient with the homozygous p.Arg472Ter variant (Philippe et al., 2009). The p.Arg472Ter is a very rare variant, reported in heterozygous state in the gnomAD (exome) database with AF=0.0032 % ( 8 alleles of 251,490). We interpret the p.Arg472Ter as a pathogenic variant.(ACMG criteria : PVS1,PP5,PM2,PP3)
Ambry Genetics RCV002512619 SCV003711996 pathogenic Inborn genetic diseases 2021-05-27 criteria provided, single submitter clinical testing The c.1708C>T (p.R570*) alteration, located in exon 9 (coding exon 9) of the TRAPPC9 gene, consists of a C to T substitution at nucleotide position 1708. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 570. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant has been identified as homozygous in three brothers from a consanguineous Tunisian family with autosomal recessive intellectual disability, mild microcephaly, and white matter abnormalities (Philippe, 2009). Expression studies showed an undetectable level of TRAPPC9 protein in patient skin fibroblasts (Philippe, 2009). Based on the available evidence, this alteration is classified as pathogenic.
OMIM RCV000000795 SCV000020945 pathogenic Intellectual disability, autosomal recessive 13 2009-12-01 no assertion criteria provided literature only

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