ATM NM_000051.3:c.3118A>G, Met1040Val

Variant summary: The ATM c.3118A>G (p.Met1040Val) variant involves the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 459/122598 control chromosomes (10 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0413846 (428/10342, 10 homozygotes). This frequency is about 10 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. Variant has been reported by multiple studies in both patients and healthy controls, supporting the non-pathogenic nature of this variant. In addition, multiple clinical diagnostic laboratories classified this variant as benign. Considering the high allele frequency of the variant and the homozygous occurrences in the African subpopulation, it was classified as Benign.

This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. 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].