11-94471593-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005591.4(MRE11):c.826C>G(p.Pro276Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.826C>G | p.Pro276Ala | missense_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.826C>G | p.Pro276Ala | missense_variant | Exon 8 of 20 | 1 | NM_005591.4 | ENSP00000325863.4 | ||
MRE11 | ENST00000323977.7 | c.826C>G | p.Pro276Ala | missense_variant | Exon 8 of 19 | 1 | ENSP00000326094.3 | |||
MRE11 | ENST00000407439.7 | c.835C>G | p.Pro279Ala | missense_variant | Exon 8 of 20 | 2 | ENSP00000385614.3 | |||
MRE11 | ENST00000393241.8 | c.826C>G | p.Pro276Ala | missense_variant | Exon 8 of 20 | 5 | ENSP00000376933.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.P276A variant (also known as c.826C>G), located in coding exon 7 of the MRE11A gene, results from a C to G substitution at nucleotide position 826. The proline at codon 276 is replaced by alanine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 120000 alleles tested) in our clinical cohort. This amino acid position is highly 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at