AMT

aminomethyltransferase, the group of Methyltransferase families

Basic information

Region (hg38): 3:49416777-49422685

Links

ENSG00000145020 ∙ NCBI:275 ∙ OMIM:238310 ∙ HGNC:473 ∙ Uniprot:P48728 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycine encephalopathy (Definitive), mode of inheritance: AR
• glycine encephalopathy (Definitive), mode of inheritance: AR
• neonatal glycine encephalopathy (Supportive), mode of inheritance: AR
• infantile glycine encephalopathy (Supportive), mode of inheritance: AR
• atypical glycine encephalopathy (Supportive), mode of inheritance: Unknown
• glycine encephalopathy (Strong), mode of inheritance: AR
• glycine encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycine encephalopathy 2	AR	Biochemical; Pharmacogenomic	There is no current effective treatment for severe disease; however, children with mutations associated with residual GCS enzyme activity treated aggressively early with sodium benzoate and N-methyl D-aspartate receptor site antagonists may have improved outcomes; Valproate should be avoided	Biochemical; Neurologic; Ophthalmologic	11139253; 12948742; 16151895; 16450403; 20301531; 19299230; 21470805; 28462797

ClinVar

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

• Non-ketotic hyperglycinemia (584 variants)
• not provided (46 variants)
• Inborn genetic diseases (23 variants)
• Glycine encephalopathy 2 (16 variants)
• not specified (15 variants)
• Neurodevelopmental delay (2 variants)
• Seizure (1 variants)
• See cases (1 variants)
• AMT-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMT 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	168	2	171
missense	4	24	149	4		181
nonsense	10	5	1			16
start loss	2	2				4
frameshift	25	21	2			48
inframe indel		1	7			8
splice donor/acceptor (+/-2bp)	5	11	2			18
splice region		2	8	31		41
non coding			15	54	8	77
Total	46	64	177	226	10

Highest pathogenic variant AF is 0.0000722

Variants in AMT

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

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

Position	Type	Phenotype	Significance	ClinVar
3-49416844-G-A		Non-ketotic hyperglycinemia	Benign (Jan 13, 2018)
3-49416862-G-C		Non-ketotic hyperglycinemia	Uncertain significance (Jan 12, 2018)
3-49416919-T-C		Non-ketotic hyperglycinemia	Uncertain significance (Jan 13, 2018)
3-49416924-G-A		Non-ketotic hyperglycinemia	Uncertain significance (Jan 13, 2018)
3-49416995-G-A		Non-ketotic hyperglycinemia	Uncertain significance (Jan 12, 2018)
3-49417116-C-G		Non-ketotic hyperglycinemia	Uncertain significance (Jan 13, 2018)
3-49417124-G-A		Non-ketotic hyperglycinemia	Likely benign (Jan 12, 2018)
3-49417133-A-G		Non-ketotic hyperglycinemia	Uncertain significance (Jan 13, 2018)
3-49417377-C-G		Non-ketotic hyperglycinemia	Uncertain significance (Jan 12, 2018)
3-49417410-C-A		Non-ketotic hyperglycinemia	Likely benign (Jan 12, 2018)
3-49417454-C-A		Non-ketotic hyperglycinemia • Inborn genetic diseases	Uncertain significance (Aug 10, 2022)
3-49417542-AC-A		Non-ketotic hyperglycinemia	Uncertain significance (Mar 10, 2021)
3-49417545-TGAG-T		Non-ketotic hyperglycinemia	Uncertain significance (Aug 04, 2023)
3-49417546-G-C		Non-ketotic hyperglycinemia	Likely benign (Jan 18, 2023)
3-49417548-G-A		Non-ketotic hyperglycinemia	Uncertain significance (Sep 27, 2022)
3-49417549-G-A		Non-ketotic hyperglycinemia	Likely benign (May 04, 2021)
3-49417550-G-T		Non-ketotic hyperglycinemia	Uncertain significance (Aug 09, 2022)
3-49417550-GTAT-ATA		Non-ketotic hyperglycinemia	Uncertain significance (Aug 02, 2017)
3-49417553-T-C		Non-ketotic hyperglycinemia	Uncertain significance (Jan 15, 2018)
3-49417553-T-G		Non-ketotic hyperglycinemia	Uncertain significance (Aug 22, 2022)
3-49417554-A-G		Non-ketotic hyperglycinemia	Uncertain significance (Aug 13, 2021)
3-49417555-G-A		Non-ketotic hyperglycinemia	Likely benign (Dec 12, 2023)
3-49417561-T-G		Non-ketotic hyperglycinemia	Likely benign (Aug 23, 2021)
3-49417562-G-T		Non-ketotic hyperglycinemia	Uncertain significance (Jun 14, 2016)
3-49417565-G-A		Non-ketotic hyperglycinemia	Uncertain significance (Jul 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMT	protein_coding	protein_coding	ENST00000273588	9	5976

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00272	0.985	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.101	244	240	1.02	0.0000149	2610
Missense in Polyphen		80	93.425	0.8563		1045
Synonymous	-0.472	101	95.1	1.06	0.00000570	861
Loss of Function	2.19	7	16.7	0.420	8.27e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000452	0.000447
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000982	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.000294	0.000294
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. {ECO:0000269|PubMed:16051266}.
• Disease: DISEASE: Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. {ECO:0000269|PubMed:10873393, ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:16051266, ECO:0000269|PubMed:26371980, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:8005589, ECO:0000269|PubMed:9600239, ECO:0000269|PubMed:9621520}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: One carbon pool by folate - Homo sapiens (human);Glycine, serine and threonine metabolism - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Ammonia Recycling;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);One Carbon Metabolism;Trans-sulfuration and one carbon metabolism;Folate metabolism;Glycine degradation;Metabolism of amino acids and derivatives;Metabolism;Vitamin B9 (folate) metabolism;Glyoxylate metabolism and glycine degradation;Glycine, serine, alanine and threonine metabolism;glycine cleavage (Consensus)

Recessive Scores

• pRec: 0.277

Intolerance Scores

• loftool: 0.0987
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.391
• hipred: N
• hipred_score: 0.473
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0200

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Amt
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; 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)

Gene ontology

• Biological process: glycine catabolic process;glycine decarboxylation via glycine cleavage system;methylation
• Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix
• Molecular function: aminomethyltransferase activity;transaminase activity