rs786202636
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_005591.4(MRE11):c.880A>G(p.Met294Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. M294T) has been classified as Uncertain significance.
Frequency
Consequence
NM_005591.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.880A>G | p.Met294Val | missense_variant | 9/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.880A>G | p.Met294Val | missense_variant | 9/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.880A>G | p.Met294Val | missense_variant | 9/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.889A>G | p.Met297Val | missense_variant | 9/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.880A>G | p.Met294Val | missense_variant | 9/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461010Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 726820
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 08, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2023 | The p.M294V variant (also known as c.880A>G), located in coding exon 8 of the MRE11A gene, results from an A to G substitution at nucleotide position 880. The methionine at codon 294 is replaced by valine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Ataxia-telangiectasia-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 294 of the MRE11 protein (p.Met294Val). This variant is present in population databases (rs786202636, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 186023). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at