11-94459488-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005591.4(MRE11):āc.1420G>Cā(p.Val474Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V474A) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1420G>C | p.Val474Leu | missense_variant | 13/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1420G>C | p.Val474Leu | missense_variant | 13/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1420G>C | p.Val474Leu | missense_variant | 13/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1429G>C | p.Val477Leu | missense_variant | 13/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1420G>C | p.Val474Leu | missense_variant | 13/20 | 5 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251356Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135850
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461762Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727180
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 08, 2023 | The p.V474L variant (also known as c.1420G>C), located in coding exon 12 of the MRE11A gene, results from a G to C substitution at nucleotide position 1420. The valine at codon 474 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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