Variant 11-4127116-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001033.5(RRM1):c.1552C>T(p.Pro518Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RRM1
NM_001033.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

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]

RRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS2

High AC in GnomAdExome4 at 6 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 linkuse as main transcript	c.1552C>T	p.Pro518Ser	missense_variant	14/19	ENST00000300738.10	NP_001024.1	P23921
RRM1	NM_001318064.1 linkuse as main transcript	c.1261C>T	p.Pro421Ser	missense_variant	13/18		NP_001304993.1	P23921B4E0I8
RRM1	NM_001330193.1 linkuse as main transcript	c.886C>T	p.Pro296Ser	missense_variant	8/13		NP_001317122.1	E9PL69
RRM1	NM_001318065.1 linkuse as main transcript	c.538C>T	p.Pro180Ser	missense_variant	8/13		NP_001304994.1	P23921B4DXD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRM1	ENST00000300738.10 linkuse as main transcript	c.1552C>T	p.Pro518Ser	missense_variant	14/19	1	NM_001033.5	ENSP00000300738.5		P23921

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251346

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727220

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

ExAC

AF:

0.0000165

AC:

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

Oct 25, 2023

The c.1552C>T (p.P518S) alteration is located in exon 14 (coding exon 14) of the RRM1 gene. This alteration results from a C to T substitution at nucleotide position 1552, causing the proline (P) at amino acid position 518 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-7.0

D;D

REVEL

Benign

0.19

Sift

Benign

0.053

T;T

Sift4G

Benign

0.081

T;T

Polyphen

0.83

P;.

Vest4

0.67

MutPred

0.49

Gain of phosphorylation at P518 (P = 0.0879);.;

MVP

0.33

MPC

0.94

ClinPred

0.83

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over