rs747832587
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_005591.4(MRE11):βc.1441delβ(p.Thr481HisfsTer43) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. T481T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_005591.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1441del | p.Thr481HisfsTer43 | frameshift_variant | 13/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1441del | p.Thr481HisfsTer43 | frameshift_variant | 13/20 | 1 | NM_005591.4 | P3 | |
MRE11 | ENST00000323977.7 | c.1441del | p.Thr481HisfsTer43 | frameshift_variant | 13/19 | 1 | |||
MRE11 | ENST00000407439.7 | c.1450del | p.Thr484HisfsTer43 | frameshift_variant | 13/20 | 2 | |||
MRE11 | ENST00000393241.8 | c.1441del | p.Thr481HisfsTer43 | frameshift_variant | 13/20 | 5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251336Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135838
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461722Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727162
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 31, 2023 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2015 | This sequence change deletes 1 nucleotide from exon 13 of the MRE11A mRNA (c.1441delA), causing a frameshift at codon 481. This creates a premature translational stop signal (p.Thr481Hisfs*43) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MRE11A are known to be pathogenic (PMID: 10612394, 11371508). For these reasons, this variant has been classified as Pathogenic. - |
Ataxia-telangiectasia-like disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2015 | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in MRE11A are known to be pathogenic (PMID: 10612394, 11371508). This sequence change deletes 1 nucleotide from exon 13 of the MRE11A mRNA (c.1441delA), causing a frameshift at codon 481. This creates a premature translational stop signal (p.Thr481Hisfs*43) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at