MGME1

mitochondrial genome maintenance exonuclease 1, the group of Exonucleases

Basic information

Region (hg38): 20:17969018-17991122

Previous symbols: [ "C20orf72" ]

Links

ENSG00000125871 ∙ NCBI:92667 ∙ OMIM:615076 ∙ HGNC:16205 ∙ Uniprot:Q9BQP7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial DNA depletion syndrome 11 (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 11 (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 11	AR	Cardiovascular	In addition to other manifestations, the condition has been described as including cardiovascular sequelae (eg, dilated cardiomyopathy, arrhythymias), and awareness may allow appropriate surveillance and prompt management	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	23313956

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MGME1 gene.

• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MGME1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				26	2	28
missense			63	5	2	70
nonsense	4	1				5
start loss			1			1
frameshift	4		2			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding				17	9	26
Total	8	1	68	48	13

Highest pathogenic variant AF is 0.0000329

Variants in MGME1

This is a list of pathogenic ClinVar variants found in the MGME1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-17969103-C-T			Likely benign (Jun 24, 2021)
20-17969679-C-T			Likely benign (Jun 28, 2018)
20-17969694-T-G			Likely benign (Jul 07, 2018)
20-17969860-A-G			Uncertain significance (Aug 04, 2023)
20-17969866-A-G		Inborn genetic diseases	Uncertain significance (Feb 08, 2023)
20-17969868-G-A			Uncertain significance (Dec 28, 2021)
20-17969871-G-C		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
20-17969882-C-G			Uncertain significance (Feb 06, 2023)
20-17969882-C-T			Uncertain significance (Dec 30, 2021)
20-17969893-CA-C			Pathogenic (Jun 27, 2022)
20-17969902-A-T		not specified • Mitochondrial DNA depletion syndrome 11	Benign (Jan 31, 2024)
20-17969903-G-A			Uncertain significance (Sep 12, 2022)
20-17969906-CAAA-C			Uncertain significance (Aug 15, 2022)
20-17969908-A-G			Uncertain significance (May 08, 2023)
20-17969911-T-C		Inborn genetic diseases	Uncertain significance (May 18, 2023)
20-17969912-TTTC-T		Mitochondrial DNA depletion syndrome 11	Uncertain significance (Aug 10, 2022)
20-17969924-C-A			Pathogenic (Feb 06, 2023)
20-17969930-C-T		Inborn genetic diseases	Uncertain significance (Aug 31, 2023)
20-17969938-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
20-17969940-T-G			Likely benign (Jul 06, 2022)
20-17969945-C-G		not specified • MGME1-related disorder	Benign/Likely benign (Jan 19, 2024)
20-17969958-C-T			Likely benign (Mar 20, 2022)
20-17969962-T-A			Uncertain significance (Oct 13, 2022)
20-17969968-C-T		Inborn genetic diseases	Uncertain significance (Jun 13, 2022)
20-17969973-G-A		MGME1-related disorder	Likely benign (Jan 09, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MGME1	protein_coding	protein_coding	ENST00000377710	4	22210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00185	0.977	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.258	187	177	1.05	0.00000812	2249
Missense in Polyphen		56	55.265	1.0133		722
Synonymous	0.674	59	66.0	0.894	0.00000306	642
Loss of Function	2.03	7	15.6	0.447	7.55e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000109	0.000109
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells. {ECO:0000255|HAMAP- Rule:MF_03030, ECO:0000269|PubMed:23313956, ECO:0000269|PubMed:23358826}.
• Disease: DISEASE: Mitochondrial DNA depletion syndrome 11 (MTDPS11) [MIM:615084]: An autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia, muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities. {ECO:0000269|PubMed:23313956}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0984

Intolerance Scores

• rvis_EVS: 0.68
• rvis_percentile_EVS: 85.04

Haploinsufficiency Scores

• pHI: 0.302
• hipred: N
• hipred_score: 0.206
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mgme1
• Phenotype: cellular phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: mitochondrial genome maintenance;mitochondrial DNA replication;mitochondrial DNA repair;nucleic acid phosphodiester bond hydrolysis
• Cellular component: mitochondrion
• Molecular function: single-stranded DNA exodeoxyribonuclease activity