11-4111632-A-G
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_001033.5(RRM1):āc.479A>Gā(p.Asn160Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000604 in 1,604,878 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 33)
Exomes š: 0.000062 ( 0 hom. )
Consequence
RRM1
NM_001033.5 missense
NM_001033.5 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 4.45
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 -3 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.11334276).
BS2
High AC in GnomAd4 at 7 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.479A>G | p.Asn160Ser | missense_variant | 6/19 | ENST00000300738.10 | NP_001024.1 | |
RRM1 | NM_001318064.1 | c.188A>G | p.Asn63Ser | missense_variant | 5/18 | NP_001304993.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RRM1 | ENST00000300738.10 | c.479A>G | p.Asn160Ser | missense_variant | 6/19 | 1 | NM_001033.5 | ENSP00000300738.5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248284Hom.: 0 AF XY: 0.0000448 AC XY: 6AN XY: 134048
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GnomAD4 exome AF: 0.0000620 AC: 90AN: 1452558Hom.: 0 Cov.: 29 AF XY: 0.0000582 AC XY: 42AN XY: 721482
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152320Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74492
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2024 | The c.479A>G (p.N160S) alteration is located in exon 6 (coding exon 6) of the RRM1 gene. This alteration results from a A to G substitution at nucleotide position 479, causing the asparagine (N) at amino acid position 160 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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