rs13447632
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005591.4(MRE11):āc.771A>Gā(p.Glu257Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 1,612,938 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_005591.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MRE11 | NM_005591.4 | c.771A>G | p.Glu257Glu | synonymous_variant | Exon 8 of 20 | ENST00000323929.8 | NP_005582.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.771A>G | p.Glu257Glu | synonymous_variant | Exon 8 of 20 | 1 | NM_005591.4 | ENSP00000325863.4 | ||
MRE11 | ENST00000323977.7 | c.771A>G | p.Glu257Glu | synonymous_variant | Exon 8 of 19 | 1 | ENSP00000326094.3 | |||
MRE11 | ENST00000407439.7 | c.780A>G | p.Glu260Glu | synonymous_variant | Exon 8 of 20 | 2 | ENSP00000385614.3 | |||
MRE11 | ENST00000393241.8 | c.771A>G | p.Glu257Glu | synonymous_variant | Exon 8 of 20 | 5 | ENSP00000376933.4 |
Frequencies
GnomAD3 genomes AF: 0.00280 AC: 426AN: 152038Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000789 AC: 198AN: 250944Hom.: 1 AF XY: 0.000619 AC XY: 84AN XY: 135616
GnomAD4 exome AF: 0.000353 AC: 515AN: 1460782Hom.: 2 Cov.: 31 AF XY: 0.000314 AC XY: 228AN XY: 726686
GnomAD4 genome AF: 0.00281 AC: 427AN: 152156Hom.: 2 Cov.: 32 AF XY: 0.00288 AC XY: 214AN XY: 74396
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Ataxia-telangiectasia-like disorder 1 Benign:3
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:3
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Variant summary: The MRE11A c.771A>G (p.Glu257Glu) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 281/276646 (2 homozygotes) control chromosomes at a frequency of 0.0010157, which is approximately 16 times the estimated maximal expected allele frequency of a pathogenic MRE11A variant (0.0000625), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign. -
MRE11: BP4, BP7 -
Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Ataxia-telangiectasia-like disorder Benign:1
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Hereditary breast ovarian cancer syndrome Benign:1
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MRE11-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at