rs2094557893

Variant names:

• chr11-4106058-A-C
• NM_001033.5:c.121A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-4106058-A-C
• chr11-4106058-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033.5(RRM1):​c.121A>C​(p.Met41Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M41V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RRM1 NM_001033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2606898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRM1	NM_001033.5	c.121A>C	p.Met41Leu	missense_variant	Exon 3 of 19	ENST00000300738.10	NP_001024.1
RRM1	NM_001318064.1	c.-5-1377A>C		intron_variant	Intron 2 of 17		NP_001304993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10	c.121A>C	p.Met41Leu	missense_variant	Exon 3 of 19	1	NM_001033.5	ENSP00000300738.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459672 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Benign	0.56	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.46
MutPred		0.40		Loss of ubiquitination at K42 (P = 0.1322);
MVP		0.31
MPC		0.79
ClinPred		0.67	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.49
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-4127288;