rs786203449
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005591.4(MRE11):c.1280T>C(p.Leu427Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,724 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. L427F) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1280T>C | p.Leu427Ser | missense_variant | 12/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1280T>C | p.Leu427Ser | missense_variant | 12/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1280T>C | p.Leu427Ser | missense_variant | 12/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1289T>C | p.Leu430Ser | missense_variant | 12/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1280T>C | p.Leu427Ser | missense_variant | 12/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250962Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135686
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461508Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727050
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 14, 2021 | The p.L427S variant (also known as c.1280T>C), located in coding exon 11 of the MRE11A gene, results from a T to C substitution at nucleotide position 1280. The leucine at codon 427 is replaced by serine, 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 | Aug 03, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 427 of the MRE11 protein (p.Leu427Ser). This variant is present in population databases (rs786203449, gnomAD 0.008%). 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: 187070). 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