ClinVar Miner

Submissions for variant NM_000036.2(AMPD1):c.133C>T (p.Gln45Ter) (rs17602729)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000487355 SCV000854814 other not provided 2018-02-07 criteria provided, single submitter clinical testing
GeneDx RCV000487355 SCV000568077 uncertain significance not provided 2019-01-09 criteria provided, single submitter clinical testing The Q45X variant in the AMPD1 gene has been reported previously in the compound heterozygous state with another AMPD1 gene variant as well as in the homozygous state in multiple, unrelated individuals with features of adenosine monophosphate deaminase deficiency (Morisaki et al., 1992; Gross et al., 2002; Castro-Gago et al., 2011). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, the Q45X variant is observed in 16,531/126,536 (13.1%) alleles from individuals of non-Finnish European background, including multiple unrelated homozygous individuals, in large population cohorts (Lek et al., 2016). Therefore, we interpret Q45X as a variant of uncertain significance.
GenomeConnect, ClinGen RCV000019933 SCV000607345 not provided Muscle AMP deaminase deficiency no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000019933 SCV000755841 uncertain significance Muscle AMP deaminase deficiency 2018-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln45*) in the AMPD1 gene. This protein was not detectable by immunostaining in an individual homozygous for this variant (PMID: 1631143). This variant is present in population databases (rs17602729, ExAC 13%). This variant has been observed to segregate with adenosine monophosphate deaminase deficiency in a single family (PMID: 1631143) and has been reported as homozygous in individuals affected with the same disease (PMID: 1631143, 8335021, 21343608). This variant is also known as c.34C>T (p.Glu12*) in the literature. ClinVar contains an entry for this variant (Variation ID: 18271). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Experimental studies have shown that this nonsense change causes a significant reduction in the enzyme activity of the protein encoded by AMPD1 (PMID: 1631143). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000487355 SCV000802453 pathogenic not provided 2016-02-19 no assertion criteria provided clinical testing
OMIM RCV000019933 SCV000040231 pathogenic Muscle AMP deaminase deficiency 2011-06-01 no assertion criteria provided literature only

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