rs1414846775
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000051.4(ATM):āc.3446A>Gā(p.Asn1149Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1149D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000051.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.3446A>G | p.Asn1149Ser | missense_variant | 24/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.3446A>G | p.Asn1149Ser | missense_variant | 24/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251178Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135788
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461376Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726992
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2017 | In summary, this variant has uncertain impact on ATM function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). This variant has not been reported in the literature in individuals with a ATM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 1149 of the ATM protein (p.Asn1149Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 28, 2021 | The p.N1149S variant (also known as c.3446A>G), located in coding exon 23 of the ATM gene, results from an A to G substitution at nucleotide position 3446. The asparagine at codon 1149 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at