11-108223183-A-AGT
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000051.4(ATM):c.-32_-31dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATM
NM_000051.4 5_prime_UTR
NM_000051.4 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0850
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.-32_-31dup | 5_prime_UTR_variant | 1/63 | ENST00000675843.1 | NP_000042.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.-32_-31dup | 5_prime_UTR_variant | 1/63 | NM_000051.4 | ENSP00000501606 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 13906Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 7524
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74444
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2017 | This variant is denoted ATM c.-32_-31dupTG, and describes a duplication in the first exon of the ATM gene, which is located within the 5' untranslated region (UTR). The surrounding sequence, with the bases that are duplicated in braces, is GCAG{TG}gtag where the capital letters are exonic and lowercase are intronic. While several in silico splicing models are uninformative an effect on splicing cannot be ruled out in the absence of RNA or functional studies. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This duplication was not observed in 1000 Genomes and this location is not covered in the NHLBI Exome Sequencing Project. At this time, we consider ATM c.-32_-31dupTG to be a variant of uncertain significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at