ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.-4C>T

gnomAD frequency: 0.00022  dbSNP: rs138350285
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000185790 SCV000238726 uncertain significance not provided 2019-03-29 criteria provided, single submitter clinical testing Previously reported in association with citrullinemia type I (Engel et al., 2009); Nucleotide substitution has no predicted effect on splicing and is not conserved across species; Alters the Kozak consensus sequence, which plays an important role in the initiation of protein translation; This variant is associated with the following publications: (PMID: 25087612, 19006241)
Invitae RCV002228803 SCV000630059 likely benign Citrullinemia 2023-09-08 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000541100 SCV001328934 uncertain significance Citrullinemia type I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab RCV000541100 SCV001737167 uncertain significance Citrullinemia type I 2021-05-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000541100 SCV002060122 uncertain significance Citrullinemia type I 2021-10-01 criteria provided, single submitter clinical testing NM_000050.4(ASS1):c.-4C>T is a 5' non-coding variant classified as a variant of uncertain significance in the context of citrullinemia type 1. c.-4C>T has been observed in a case with relevant disease (PMID: 28111830). Functional assessments of this variant are not available in the literature. c.-4C>T has been observed in population frequency databases (gnomAD: SAS 0.18%). In summary, there is insufficient evidence to classify NM_000050.4(ASS1):c.-4C>T as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230438 SCV003928990 uncertain significance not specified 2023-04-13 criteria provided, single submitter clinical testing Variant summary: ASS1 c.-4C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00056 in 250834 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ASS1 causing Citrullinemia Type I (0.00056 vs 0.0041), allowing no conclusion about variant significance. The variant was reported in the literature without strong evidence for causality. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=5), Likely Pathogenic (n=1) and Likely Benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000185790 SCV001447739 likely pathogenic not provided 2020-10-23 flagged submission clinical testing
Natera, Inc. RCV000541100 SCV002082214 uncertain significance Citrullinemia type I 2021-06-21 no assertion criteria provided clinical testing

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