ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.3283A>C (p.Arg1095=) (rs876660302)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213488 SCV000277617 likely benign Hereditary cancer-predisposing syndrome 2015-08-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Color RCV000213488 SCV000913987 likely benign Hereditary cancer-predisposing syndrome 2017-03-24 criteria provided, single submitter clinical testing
GeneDx RCV000237018 SCV000294028 uncertain significance not provided 2016-03-02 criteria provided, single submitter clinical testing This variant is denoted ATM c.3283A>C at the cDNA level. This variant is silent at the coding level, preserving an Arginine at codon 1095. Multiple splicing models suggest that this variant weakens the nearby splice donor site; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM c.3283A>C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, an adenine (A) at base 3283, is conserved across species. Based on currently available information, it is unclear whether ATM c.3283A>C is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000822256 SCV000963049 uncertain significance Ataxia-telangiectasia syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change affects codon 1095 of the ATM mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the ATM protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 233274). 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. 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.

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