GNMT

glycine N-methyltransferase, the group of 7BS small molecule methyltransferases

Basic information

Region (hg38): 6:42960754-42963880

Links

ENSG00000124713 ∙ NCBI:27232 ∙ OMIM:606628 ∙ HGNC:4415 ∙ Uniprot:Q14749 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycine N-methyltransferase deficiency (Strong), mode of inheritance: AR
• glycine N-methyltransferase deficiency (Limited), mode of inheritance: Unknown
• glycine N-methyltransferase deficiency (Limited), mode of inheritance: AR
• glycine N-methyltransferase deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycine N-methyltransferase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Gastrointestinal	11596649; 11810299

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNMT 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				17	2	19
missense			50	1	1	52
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				7	11	18
Total	0	0	52	25	14

Variants in GNMT

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

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

Position	Type	Phenotype	Significance	ClinVar
6-42960777-A-G			Uncertain significance (Oct 15, 2019)
6-42960779-C-T		GNMT-related disorder	Benign (Dec 30, 2023)
6-42960792-C-G			Uncertain significance (Feb 14, 2019)
6-42960805-T-G			Uncertain significance (Feb 08, 2022)
6-42960808-C-G			Uncertain significance (Jun 14, 2023)
6-42960816-G-A		not specified	Uncertain significance (Jan 03, 2024)
6-42960828-C-T			Uncertain significance (Nov 17, 2022)
6-42960843-G-A			Uncertain significance (Jan 09, 2024)
6-42960849-G-A			Uncertain significance (Dec 30, 2023)
6-42960851-G-A			Likely benign (Nov 12, 2022)
6-42960855-G-A		not specified	Uncertain significance (Jun 26, 2023)
6-42960868-A-G		not specified	Uncertain significance (Feb 28, 2024)
6-42960878-C-G			Uncertain significance (Nov 16, 2021)
6-42960880-C-A			Uncertain significance (Jul 29, 2023)
6-42960909-T-C			Uncertain significance (May 30, 2022)
6-42960914-G-A			Likely benign (Aug 02, 2023)
6-42960916-T-C		Glycine N-methyltransferase deficiency	Pathogenic (Jan 01, 2002)
6-42960934-A-G			Uncertain significance (Dec 03, 2021)
6-42960952-T-C			Uncertain significance (Aug 14, 2023)
6-42960955-A-AC			Uncertain significance (Jul 11, 2023)
6-42960956-C-T			Likely benign (Jun 14, 2018)
6-42960958-T-C			Uncertain significance (Jul 17, 2023)
6-42960961-C-T		not specified	Uncertain significance (Nov 14, 2023)
6-42960968-C-G			Likely benign (Jul 26, 2023)
6-42960970-C-T			Uncertain significance (Oct 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNMT	protein_coding	protein_coding	ENST00000372808	6	3123

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00282	0.945	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.354	159	172	0.924	0.0000101	1904
Missense in Polyphen		51	58.938	0.86531		658
Synonymous	1.38	60	75.2	0.798	0.00000485	590
Loss of Function	1.70	6	12.5	0.482	5.38e-7	148

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000549	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the methylation of glycine by using S- adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine. {ECO:0000269|PubMed:15340920, ECO:0000269|PubMed:17660255}.
• Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;sarcosine oncometabolite pathway ;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);One carbon metabolism and related pathways;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Selenoamino acid metabolism;Metabolism of ingested SeMet, Sec, MeSec into H2Se;Glyoxylate metabolism and glycine degradation (Consensus)

Recessive Scores

• pRec: 0.318

Intolerance Scores

• loftool: 0.379
• rvis_EVS: 0.06
• rvis_percentile_EVS: 58.53

Haploinsufficiency Scores

• pHI: 0.754
• hipred: Y
• hipred_score: 0.644
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gnmt
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype; liver/biliary system phenotype; neoplasm

Gene ontology

• Biological process: glycogen metabolic process;regulation of gluconeogenesis;cellular protein modification process;methionine metabolic process;one-carbon metabolic process;methylation;cellular nitrogen compound metabolic process;S-adenosylhomocysteine metabolic process;S-adenosylmethionine metabolic process;protein homotetramerization;sarcosine metabolic process
• Cellular component: cytosol
• Molecular function: protein binding;folic acid binding;glycine binding;glycine N-methyltransferase activity;identical protein binding;S-adenosyl-L-methionine binding