NM_001033.5:c.1142G>A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong
The NM_001033.5(RRM1):c.1142G>A(p.Arg381His) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_001033.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RRM1 | NM_001033.5 | c.1142G>A | p.Arg381His | missense_variant | Exon 12 of 19 | ENST00000300738.10 | NP_001024.1 | |
RRM1 | NM_001318064.1 | c.851G>A | p.Arg284His | missense_variant | Exon 11 of 18 | NP_001304993.1 | ||
RRM1 | NM_001330193.1 | c.476G>A | p.Arg159His | missense_variant | Exon 6 of 13 | NP_001317122.1 | ||
RRM1 | NM_001318065.1 | c.128G>A | p.Arg43His | missense_variant | Exon 6 of 13 | NP_001304994.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727206
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74236
ClinVar
Submissions by phenotype
Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 Pathogenic:2
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RRM1-related disorder Pathogenic:1
The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest no damaging effect of the variant on gene or gene product (REVEL: 0.26; 3Cnet: 0.01). The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV002444243 / PMID: 35617047). A different missense change at the same codon (p.Arg381Cys) has been reported to be associated with RRM1-related disorder (ClinVar ID: VCV002664486 / PMID: 35617047). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at