MGMT

O-6-methylguanine-DNA methyltransferase, the group of Methyltransferase families

Basic information

Region (hg38): 10:129467189-129770983

Links

ENSG00000170430 ∙ NCBI:4255 ∙ OMIM:156569 ∙ HGNC:7059 ∙ Uniprot:P16455 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (14 variants)
• not provided (6 variants)
• not specified (1 variants)
• Glioblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MGMT 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			1	3		4
missense			13	2	1	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	5	1

Variants in MGMT

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

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

Position	Type	Phenotype	Significance	ClinVar
10-129467245-C-T			Likely benign (May 09, 2018)
10-129467249-G-T		not specified	Uncertain significance (Nov 17, 2023)
10-129467255-C-G		not specified	Uncertain significance (Dec 03, 2021)
10-129467281-C-T		Glioblastoma	not provided (Mar 10, 2016)
10-129536278-G-T		not specified	Uncertain significance (Sep 26, 2023)
10-129536279-C-T			Uncertain significance (Feb 25, 2016)
10-129536326-A-G		not specified	Uncertain significance (May 18, 2022)
10-129536340-G-A		not specified	Likely benign (Dec 31, 2019)
10-129536349-C-T		not specified	Uncertain significance (Aug 15, 2023)
10-129707922-G-A			Likely benign (Nov 03, 2018)
10-129707936-C-T		not specified	Uncertain significance (Feb 13, 2024)
10-129707992-G-A		not specified	Uncertain significance (Dec 08, 2021)
10-129708007-C-G		not specified	Uncertain significance (Jun 01, 2023)
10-129708010-G-A		not specified	Uncertain significance (Mar 24, 2023)
10-129708014-C-T		not specified	Uncertain significance (Jul 09, 2021)
10-129708026-A-G		not specified	Uncertain significance (Mar 29, 2022)
10-129708030-C-T			Likely benign (Dec 31, 2019)
10-129759211-C-G		not specified	Uncertain significance (Jan 26, 2022)
10-129759214-G-A		not specified	Uncertain significance (Dec 16, 2023)
10-129759304-C-G		not specified	Uncertain significance (Oct 06, 2023)
10-129766794-A-G		not specified	Uncertain significance (Dec 26, 2023)
10-129766830-G-A		not specified	Uncertain significance (Jan 26, 2023)
10-129766873-G-C		not specified	Uncertain significance (Sep 16, 2021)
10-129766906-A-G			Benign (Oct 07, 2019)
10-129766915-T-C		not specified	Uncertain significance (Jun 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MGMT	protein_coding	protein_coding	ENST00000306010	5	300824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.18e-7	0.109	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.623	165	144	1.15	0.00000865	1482
Missense in Polyphen		50	47.677	1.0487		513
Synonymous	-0.992	78	67.6	1.15	0.00000490	513
Loss of Function	-0.342	10	8.90	1.12	3.81e-7	104

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.0000656	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
• Pathway: Busulfan Pathway, Pharmacodynamics;Cyclophosphamide Pathway, Pharmacodynamics;DNA Repair;MGMT-mediated DNA damage reversal;DNA Damage Reversal (Consensus)

Recessive Scores

• pRec: 0.553

Intolerance Scores

• loftool: 0.823
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.25

Haploinsufficiency Scores

• pHI: 0.0515
• hipred: N
• hipred_score: 0.438
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.572

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mgmt
• Phenotype: respiratory system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: DNA ligation;DNA repair;DNA methylation;DNA dealkylation involved in DNA repair;cellular response to oxidative stress;negative regulation of apoptotic process;regulation of cysteine-type endopeptidase activity involved in apoptotic process;response to ethanol;response to folic acid;mammary gland epithelial cell differentiation;cellular response to organic cyclic compound;cellular response to ionizing radiation;positive regulation of double-strand break repair
• Cellular component: nucleus;nucleoplasm;membrane
• Molecular function: DNA binding;methylated-DNA-[protein]-cysteine S-methyltransferase activity;calcium ion binding;methyltransferase activity;DNA-methyltransferase activity