rs587782742
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005591.4(MRE11):c.826C>T(p.Pro276Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,612,230 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. P276A) has been classified as Uncertain significance.
Frequency
Consequence
NM_005591.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.826C>T | p.Pro276Ser | missense_variant | 8/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.826C>T | p.Pro276Ser | missense_variant | 8/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.826C>T | p.Pro276Ser | missense_variant | 8/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.835C>T | p.Pro279Ser | missense_variant | 8/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.826C>T | p.Pro276Ser | missense_variant | 8/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151884Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250784Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135590
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1460346Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27AN XY: 726490
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151884Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74176
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 22, 2019 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2023 | The p.P276S variant (also known as c.826C>T), located in coding exon 7 of the MRE11A gene, results from a C to T substitution at nucleotide position 826. The proline at codon 276 is replaced by serine, an amino acid with similar properties. This variant was reported in 1/1824 patients with triple negative breast cancer, who were unselected for family history of breast or ovarian cancer (Couch FJ et al. J. Clin. Oncol. 2015 Feb;33:304-11). This alteration was also reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J. Med. Genet. 2016 Jun;53:366-76). 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. - |
Ataxia-telangiectasia-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 276 of the MRE11 protein (p.Pro276Ser). This variant is present in population databases (rs587782742, gnomAD 0.002%). This missense change has been observed in individual(s) with breast cancer (PMID: 25452441). ClinVar contains an entry for this variant (Variation ID: 142818). 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