ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.4658A>C (p.Glu1553Ala)

gnomAD frequency: 0.00007  dbSNP: rs587778075
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166074 SCV000216837 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-04 criteria provided, single submitter clinical testing The p.E1553A variant (also known as c.4658A>C), located in coding exon 30 of the ATM gene, results from an A to C substitution at nucleotide position 4658. The glutamic acid at codon 1553 is replaced by alanine, an amino acid with dissimilar properties. This alteration has been identified in an individual diagnosed with breast cancer (Tung N et al. Cancer, 2015 Jan;121:25-33). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000200014 SCV000254113 uncertain significance Ataxia-telangiectasia syndrome 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1553 of the ATM protein (p.Glu1553Ala). This variant is present in population databases (rs587778075, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 133620). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV000656761 SCV000292470 uncertain significance not provided 2023-12-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 25186627, 35534704, 35980532)
Counsyl RCV000200014 SCV000796237 uncertain significance Ataxia-telangiectasia syndrome 2017-12-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000166074 SCV000906622 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with alanine at codon 1553 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 25186627) and in an unafffected individual (PMID: 24728327). This variant has been identified in 3/280194 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV000200014 SCV001138508 uncertain significance Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120140 SCV002069333 uncertain significance not specified 2018-07-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV003467069 SCV004208241 uncertain significance Familial cancer of breast 2023-10-17 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003467069 SCV005084021 likely benign Familial cancer of breast 2024-05-20 criteria provided, single submitter clinical testing This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
ITMI RCV000120140 SCV000084280 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000200014 SCV001462334 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.