11-4123205-C-T

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

Scores

5
5
9

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.43
Variant links:
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]

Genome browser will be placed here

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
RRM1NM_001033.5 linkuse as main transcriptc.1141C>T p.Arg381Cys missense_variant 12/19 ENST00000300738.10 NP_001024.1 P23921
RRM1NM_001318064.1 linkuse as main transcriptc.850C>T p.Arg284Cys missense_variant 11/18 NP_001304993.1 P23921B4E0I8
RRM1NM_001330193.1 linkuse as main transcriptc.475C>T p.Arg159Cys missense_variant 6/13 NP_001317122.1 E9PL69
RRM1NM_001318065.1 linkuse as main transcriptc.127C>T p.Arg43Cys missense_variant 6/13 NP_001304994.1 P23921B4DXD1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RRM1ENST00000300738.10 linkuse as main transcriptc.1141C>T p.Arg381Cys missense_variant 12/191 NM_001033.5 ENSP00000300738.5 P23921

Frequencies

GnomAD3 genomes
AF:
0.0000790
AC:
12
AN:
151856
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000591
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000115
AC:
29
AN:
251430
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461800
Hom.:
0
Cov.:
31
AF XY:
0.0000358
AC XY:
26
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000581
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000790
AC:
12
AN:
151974
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000590
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000474
Bravo
AF:
0.0000680
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7

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 providedliterature onlyOMIMDec 07, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Pathogenic
3.0
M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-6.3
D;D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.065
T;T
Polyphen
0.13
B;.
Vest4
0.60
MVP
0.21
MPC
1.7
ClinPred
0.95
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.89
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141634151; hg19: chr11-4144435; API