TGS1

trimethylguanosine synthase 1, the group of 7BS DNA/RNA methyltransferases

Basic information

Region (hg38): 8:55773446-55826445

Previous symbols: [ "NCOA6IP" ]

Links

ENSG00000137574 ∙ NCBI:96764 ∙ OMIM:606461 ∙ HGNC:17843 ∙ Uniprot:Q96RS0 ∙ 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 TGS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGS1 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	2	3
missense			41	4	9	54
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	41	5	11

Variants in TGS1

This is a list of pathogenic ClinVar variants found in the TGS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-55773649-G-C		not specified	Uncertain significance (May 09, 2023)
8-55773673-C-G		not specified	Uncertain significance (Dec 17, 2023)
8-55773677-A-T		not specified	Uncertain significance (Oct 05, 2021)
8-55782760-G-T		not specified	Uncertain significance (Jan 31, 2022)
8-55782801-G-A		not specified	Likely benign (Jan 23, 2024)
8-55782806-A-T		not specified	Uncertain significance (May 13, 2024)
8-55785748-G-C		not specified	Uncertain significance (Sep 07, 2022)
8-55785806-G-A			Benign (Jul 02, 2018)
8-55785834-G-A		not specified	Uncertain significance (May 14, 2024)
8-55785874-G-C		not specified	Uncertain significance (Dec 28, 2022)
8-55785875-C-A		not specified	Uncertain significance (Mar 25, 2024)
8-55785877-C-T		not specified	Uncertain significance (Sep 27, 2022)
8-55786265-A-G			Benign (Feb 26, 2018)
8-55786314-A-C		not specified	Uncertain significance (Nov 08, 2022)
8-55786346-G-A			Benign/Likely benign (Nov 01, 2022)
8-55786376-A-G			Benign (May 18, 2018)
8-55786454-A-C		not specified	Uncertain significance (Apr 25, 2023)
8-55786506-A-G		not specified	Uncertain significance (Dec 16, 2023)
8-55786547-A-G		not specified	Uncertain significance (Oct 20, 2023)
8-55786554-C-T		not specified	Uncertain significance (Jan 30, 2024)
8-55786564-A-C			Likely benign (Dec 01, 2022)
8-55786566-T-G		not specified	Uncertain significance (May 13, 2022)
8-55786667-G-T		not specified	Uncertain significance (Nov 29, 2023)
8-55786673-G-A		not specified	Uncertain significance (Jun 11, 2021)
8-55786683-T-C		not specified	Uncertain significance (Apr 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGS1	protein_coding	protein_coding	ENST00000260129	13	52307

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.10e-12	0.902	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.16	503	435	1.16	0.0000207	5682
Missense in Polyphen		147	136.76	1.0749		1748
Synonymous	-0.285	158	154	1.03	0.00000780	1496
Loss of Function	2.01	25	38.4	0.650	0.00000169	531

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000758	0.000757
Ashkenazi Jewish	0.00	0.00
East Asian	0.000331	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000274	0.000273
Middle Eastern	0.000331	0.000326
South Asian	0.000503	0.000490
Other	0.000658	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation. {ECO:0000269|PubMed:11517327, ECO:0000269|PubMed:11912212, ECO:0000269|PubMed:16687569, ECO:0000269|PubMed:18775984}.
• Pathway: RNA transport - Homo sapiens (human);Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;snRNP Assembly;Metabolism of RNA;Metabolism;Phosphatidylinositol phosphate metabolism;Metabolism of non-coding RNA (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.885
• rvis_EVS: 2.61
• rvis_percentile_EVS: 98.77

Haploinsufficiency Scores

• pHI: 0.287
• hipred: Y
• hipred_score: 0.537
• ghis: 0.465

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.518

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tgs1
• Phenotype: growth/size/body region phenotype; cellular phenotype; 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: spliceosomal snRNP assembly;7-methylguanosine RNA capping;regulation of lipid metabolic process;ribonucleoprotein complex biogenesis;7-methylguanosine cap hypermethylation
• Cellular component: extracellular space;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;Cajal body;small nuclear ribonucleoprotein complex
• Molecular function: protein binding;RNA methyltransferase activity;RNA trimethylguanosine synthase activity