11-108297401-C-G
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000051.4(ATM):c.5005+19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,408,198 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: not found (cov: 33)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
ATM
NM_000051.4 intron
NM_000051.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.650
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 11-108297401-C-G is Benign according to our data. Variant chr11-108297401-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 420913.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.5005+19C>G | intron_variant | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.5005+19C>G | intron_variant | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249770Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135086
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GnomAD4 exome AF: 0.00000497 AC: 7AN: 1408198Hom.: 0 Cov.: 25 AF XY: 0.00000569 AC XY: 4AN XY: 703598
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2017 | This variant is denoted ATM c.5005+19C>G or IVS33+19C>G and consists of a C>G nucleotide substitution at the +19 position of intron 33 of the ATM gene. Multiple in silico models predict this variant to create a cryptic splice donor site and possibly causing abnormal gene splicing. 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.5005+19C>G was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). The cytosine (C) nucleotide that is altered is not conserved. Based on currently available evidence, it is unclear whether ATM c.5005+19C>G is pathogenic or benign. We consider it to be a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 08, 2020 | This variant causes a C to G nucleotide substitution at the +19 position of intron 33 of the ATM gene. Splice site prediction tools predict that this variant may impact RNA splicing due to the creation of a new splice donor site. To our knowledge, this prediction has not been investigated in published RNA studies. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/249770 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Ataxia-telangiectasia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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DS_DG_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at