rs786203158
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005591.4(MRE11):āc.1478T>Gā(p.Leu493Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,888 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 (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L493L) has been classified as Likely benign.
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.1478T>G | p.Leu493Arg | missense_variant | 13/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1478T>G | p.Leu493Arg | missense_variant | 13/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1478T>G | p.Leu493Arg | missense_variant | 13/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1487T>G | p.Leu496Arg | missense_variant | 13/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1478T>G | p.Leu493Arg | missense_variant | 13/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727154
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 21, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 29, 2021 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 02, 2024 | The p.L493R variant (also known as c.1478T>G), located in coding exon 12 of the MRE11A gene, results from a T to G substitution at nucleotide position 1478. The leucine at codon 493 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well 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 | Invitae | Sep 25, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 493 of the MRE11 protein (p.Leu493Arg). This variant is not present in population databases (gnomAD no frequency). 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: 186706). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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