11-4123205-C-T
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting
The NM_001033.5(RRM1):c.1141C>T(p.Arg381Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
RRM1
NM_001033.5 missense
NM_001033.5 missense
Scores
5
5
9
Clinical Significance
Conservation
PhyloP100: 5.43
Genes affected
RRM1 (HGNC:10451): (ribonucleotide reductase catalytic subunit M1) This gene encodes the large and catalytic subunit of ribonucleotide reductase, an enzyme essential for the conversion of ribonucleotides into deoxyribonucleotides. A pool of available deoxyribonucleotides is important for DNA replication during S phase of the cell cycle as well as multiple DNA repair processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP5
Variant 11-4123205-C-T is Pathogenic according to our data. Variant chr11-4123205-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2664486.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.19884562). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAd4 at 12 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RRM1 | NM_001033.5 | c.1141C>T | p.Arg381Cys | missense_variant | 12/19 | ENST00000300738.10 | NP_001024.1 | |
RRM1 | NM_001318064.1 | c.850C>T | p.Arg284Cys | missense_variant | 11/18 | NP_001304993.1 | ||
RRM1 | NM_001330193.1 | c.475C>T | p.Arg159Cys | missense_variant | 6/13 | NP_001317122.1 | ||
RRM1 | NM_001318065.1 | c.127C>T | p.Arg43Cys | missense_variant | 6/13 | NP_001304994.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RRM1 | ENST00000300738.10 | c.1141C>T | p.Arg381Cys | missense_variant | 12/19 | 1 | NM_001033.5 | ENSP00000300738.5 |
Frequencies
GnomAD3 genomes AF: 0.0000790 AC: 12AN: 151856Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000115 AC: 29AN: 251430Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135900
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GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727216
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GnomAD4 genome AF: 0.0000790 AC: 12AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74268
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 07, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at