rs767684060
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_005591.4(MRE11):āc.946A>Gā(p.Asn316Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N316N) has been classified as Likely benign.
Frequency
Consequence
NM_005591.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.946A>G | p.Asn316Asp | missense_variant | 9/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.946A>G | p.Asn316Asp | missense_variant | 9/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.946A>G | p.Asn316Asp | missense_variant | 9/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.955A>G | p.Asn319Asp | missense_variant | 9/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.946A>G | p.Asn316Asp | missense_variant | 9/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251068Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135712
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460986Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726804
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74302
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 16, 2023 | - - |
Ataxia-telangiectasia-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces asparagine with aspartic acid at codon 316 of the MRE11 protein (p.Asn316Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs767684060, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2020 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at