rs786202307
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005591.4(MRE11):c.259C>T(p.Arg87Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R87Q) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.259C>T | p.Arg87Trp | missense_variant | 4/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.259C>T | p.Arg87Trp | missense_variant | 4/20 | 1 | NM_005591.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151958Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251094Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135714
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461506Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727040
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74328
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 20, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 01, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2023 | The p.R87W variant (also known as c.259C>T), located in coding exon 3 of the MRE11A gene, results from a C to T substitution at nucleotide position 259. The arginine at codon 87 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Dec 22, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 87 of the MRE11 protein (p.Arg87Trp). This variant is present in population databases (rs758112386, gnomAD 0.02%). 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: 185603). 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 disruptive. 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