Submissions for variant NM_000051.4(ATM):c.5178-3del

dbSNP: rs1555105575

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000628215	SCV000749109	uncertain significance	Ataxia-telangiectasia syndrome	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change falls in intron 34 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). 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: 524427). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Baylor Genetics	RCV003465379	SCV004212035	uncertain significance	Familial cancer of breast	2023-03-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004025313	SCV005017775	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-11	criteria provided, single submitter	clinical testing	The c.5178-3delC intronic variant, located in intron 33 of the ATM gene, results from a deletion of one nucleotide within intron 33 of the ATM gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site. Based on the available evidence, the clinical significance of this alteration remains unclear.