rs766182900
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_005591.4(MRE11):c.1138C>T(p.Arg380Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,728 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. R380H) 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.1138C>T | p.Arg380Cys | missense_variant | 11/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1138C>T | p.Arg380Cys | missense_variant | 11/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1138C>T | p.Arg380Cys | missense_variant | 11/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1147C>T | p.Arg383Cys | missense_variant | 11/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1138C>T | p.Arg380Cys | missense_variant | 11/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251236Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135806
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727128
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74294
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2023 | The p.R380C variant (also known as c.1138C>T), located in coding exon 10 of the MRE11A gene, results from a C to T substitution at nucleotide position 1138. The arginine at codon 380 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 | Nov 28, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 380 of the MRE11 protein (p.Arg380Cys). This variant is present in population databases (rs766182900, 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: 230357). 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