rs372657126
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005591.4(MRE11):āc.1190A>Gā(p.His397Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,600 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H397P) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1190A>G | p.His397Arg | missense_variant | 11/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1190A>G | p.His397Arg | missense_variant | 11/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1190A>G | p.His397Arg | missense_variant | 11/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1199A>G | p.His400Arg | missense_variant | 11/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1190A>G | p.His397Arg | missense_variant | 11/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251286Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135828
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727110
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 17, 2015 | The p.H397R variant (also known as c.1190A>G), located in coding exon 10 of the MRE11A gene, results from an A to G substitution at nucleotide position 1190. The histidine at codon 397 is replaced by arginine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs372657126. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele has an overall frequency of approximately 0.01% (1/12998) total alleles studied and 0.01% (1/8596) European American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. 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 p.H397R remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at