11-94437220-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_005591.4(MRE11):c.1883G>A(p.Arg628Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1883G>A | p.Arg628Lys | missense_variant | 17/20 | ENST00000323929.8 | NP_005582.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1883G>A | p.Arg628Lys | missense_variant | 17/20 | 1 | NM_005591.4 | ENSP00000325863.4 | ||
MRE11 | ENST00000323977.7 | c.1799G>A | p.Arg600Lys | missense_variant | 16/19 | 1 | ENSP00000326094.3 | |||
MRE11 | ENST00000407439.7 | c.1892G>A | p.Arg631Lys | missense_variant | 17/20 | 2 | ENSP00000385614.3 | |||
MRE11 | ENST00000393241.8 | c.1880G>A | p.Arg627Lys | missense_variant | 17/20 | 5 | ENSP00000376933.4 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250978Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135670
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460572Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 726562
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74436
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 15, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 01, 2022 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2023 | The p.R628K variant (also known as c.1883G>A), located in coding exon 16 of the MRE11A gene, results from a G to A substitution at nucleotide position 1883. The arginine at codon 628 is replaced by lysine, 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. - |
Ataxia-telangiectasia-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 28, 2023 | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 628 of the MRE11 protein (p.Arg628Lys). This variant is present in population databases (rs587781835, gnomAD 0.007%). 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: 141551). 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