rs375223186
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS2_Supporting
The NM_005591.4(MRE11):c.1162C>T(p.Arg388Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,616 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. R388P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005591.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1162C>T | p.Arg388Trp | missense_variant | 11/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1162C>T | p.Arg388Trp | missense_variant | 11/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1162C>T | p.Arg388Trp | missense_variant | 11/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1171C>T | p.Arg391Trp | missense_variant | 11/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1162C>T | p.Arg388Trp | missense_variant | 11/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 152008Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251236Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135788
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461608Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21AN XY: 727114
GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 152008Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74240
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 20, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The p.R388W variant (also known as c.1162C>T), located in coding exon 10 of the MRE11A gene, results from a C to T substitution at nucleotide position 1162. The arginine at codon 388 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 | Sep 26, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 388 of the MRE11 protein (p.Arg388Trp). This variant is present in population databases (rs375223186, 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: 187636). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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