rs781578507
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000051.4(ATM):c.1381G>A(p.Glu461Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,866 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E461G) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.1381G>A | p.Glu461Lys | missense_variant | 10/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.1381G>A | p.Glu461Lys | missense_variant | 10/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251420Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135882
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461866Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3AN XY: 727228
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 570213). This missense change has been observed to co-occur in individuals with a different variant in ATM that has been determined to be pathogenic (Invitae), but the significance of this finding is unclear. This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is present in population databases (rs781578507, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 461 of the ATM protein (p.Glu461Lys). - |
Familial cancer of breast Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at