NM_001033.5(RRM1):c.1142G>A (p.Arg381His) AND Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 7, 2023
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003447337.2

Allele description [Variation Report for NM_001033.5(RRM1):c.1142G>A (p.Arg381His)]

NM_001033.5(RRM1):c.1142G>A (p.Arg381His)

Gene:

RRM1:ribonucleotide reductase catalytic subunit M1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_001033.5(RRM1):c.1142G>A (p.Arg381His)

HGVS:

NC_000011.10:g.4123206G>A
NG_027992.2:g.33513G>A
NM_001033.5:c.1142G>AMANE SELECT
NM_001318064.1:c.851G>A
NM_001318065.1:c.128G>A
NM_001330193.1:c.476G>A
NP_001024.1:p.Arg381His
NP_001304993.1:p.Arg284His
NP_001304994.1:p.Arg43His
NP_001317122.1:p.Arg159His
LRG_324t1:c.1142G>A
LRG_324:g.33513G>A
LRG_324p1:p.Arg381His
NC_000011.9:g.4144436G>A

Protein change:

R159H; ARG381HIS

Links:

OMIM: 180410.0001

Molecular consequence:

NM_001033.5:c.1142G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318064.1:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318065.1:c.128G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330193.1:c.476G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 6
Identifiers:: MONDO: MONDO:0957993; MedGen: C5882731; OMIM: 620647

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004174823	OMIM	no assertion criteria provided	Pathogenic (Dec 7, 2023)	germline	literature only	Shintaku, J., Pernice, W. M., Eyaid, W., Gc, J. B., Brown, Z. P., Juanola-Falgarona, M., Torres-Torronteras, J., Sommerville, E. W., Hellebrekers, D. M., Blakely, E. L., Donaldson, A., van de Laar, I., and 12 others RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J. Clin. Invest. 132: e145660, 2022.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004174823

OMIM

no assertion criteria provided

Pathogenic
(Dec 7, 2023)

germline

literature only

Shintaku, J., Pernice, W. M., Eyaid, W., Gc, J. B., Brown, Z. P., Juanola-Falgarona, M., Torres-Torronteras, J., Sommerville, E. W., Hellebrekers, D. M., Blakely, E. L., Donaldson, A., van de Laar, I., and 12 others RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. J. Clin. Invest. 132: e145660, 2022.

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Details of each submission

From OMIM, SCV004174823.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

In 2 patients (patients 1a and 1b) from a consanguineous Saudi Arabian family with autosomal recessive progressive external ophthalmoplegia-6 (PEOB6; 620647), Shintaku et al. (2022) identified homozygosity for a c.1142G-A transition (c.1142G-A, NM_001033.5) in the RRM1 gene, resulting in an arg381-to-his (R381H) substitution. The mutation, which was identified by whole-exome sequencing, segregated with disease in the family. The mutation was not present in the gnomAD database (v2.1.1). Ribonucleotide reductase activity was reduced in fibroblasts from the patients, and mtDNA was reduced in proliferating fibroblasts from the patients.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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