rs148590073
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000051.4(ATM):āc.370A>Gā(p.Ile124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000372 in 1,612,068 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000051.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.370A>G | p.Ile124Val | missense_variant | 5/63 | ENST00000675843.1 | NP_000042.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.370A>G | p.Ile124Val | missense_variant | 5/63 | NM_000051.4 | ENSP00000501606.1 |
Frequencies
GnomAD3 genomes AF: 0.00196 AC: 299AN: 152226Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000593 AC: 149AN: 251154Hom.: 0 AF XY: 0.000420 AC XY: 57AN XY: 135752
GnomAD4 exome AF: 0.000206 AC: 301AN: 1459724Hom.: 2 Cov.: 30 AF XY: 0.000183 AC XY: 133AN XY: 726316
GnomAD4 genome AF: 0.00196 AC: 299AN: 152344Hom.: 1 Cov.: 33 AF XY: 0.00184 AC XY: 137AN XY: 74502
ClinVar
Submissions by phenotype
not provided Benign:8
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 31, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 14, 2021 | This variant is associated with the following publications: (PMID: 22952040, 11505391, 17333338, 19781682, 12673804, 25980754, 12552559) - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 30, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 30, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2024 | ATM: BP1, BP2, BP4, BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 07, 2017 | Variant summary: The ATM c.370A>G (p.Ile124Val) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant . This variant was found in 93/126020 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.007634 (79/10348). This frequency is about 8 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This missense mutation has been observed in cancer patients without significant evidence for a causal role in disease (e.g. co-segregation data were not provided). In at least one ataxia-telangiectasia patient the variant co-occured with two other mutations predicted to be causative for ataxia-telangiectasia (Buzin_2003). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign, and most peer reviewed publications consider the variant a polymorphism. Taken together, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 23, 2021 | - - |
Ataxia-telangiectasia syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jan 19, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 10, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 04, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 07, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial cancer of breast Benign:2
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 19, 2024 | 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]. - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at