Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
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, |
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 |