11-108253955-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000051.4(ATM):c.2040C>T(p.Phe680=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
ATM
NM_000051.4 synonymous
NM_000051.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP6
?
Variant 11-108253955-C-T is Benign according to our data. Variant chr11-108253955-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 136436.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=7, Uncertain_significance=1}. Variant chr11-108253955-C-T is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.2040C>T | p.Phe680= | synonymous_variant | 13/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.2040C>T | p.Phe680= | synonymous_variant | 13/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461766Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727180
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 31, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 30, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 01, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2014 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 12, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 28, 2022 | - - |
Ataxia-telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at