TYW1

tRNA-yW synthesizing protein 1 homolog, the group of Radical S-adenosylmethionine domain containing

Basic information

Region (hg38): 7:66995172-67239514

Previous symbols: [ "RSAFD1" ]

Links

ENSG00000198874 ∙ NCBI:55253 ∙ OMIM:611243 ∙ HGNC:25598 ∙ Uniprot:Q9NV66 ∙ 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 TYW1 gene.

• Inborn genetic diseases (30 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYW1 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				2		2
missense			29	1	1	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	29	3	2

Variants in TYW1

This is a list of pathogenic ClinVar variants found in the TYW1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-66995210-A-G			Benign (Mar 03, 2015)
7-66995287-C-G		Shwachman-Diamond syndrome 1	Uncertain significance (May 02, 2023)
7-66995289-C-T		Aplastic anemia	Likely pathogenic (Oct 10, 2022)
7-66995291-C-A		not specified	Conflicting classifications of pathogenicity (Apr 24, 2023)
7-66995297-TC-T		Shwachman-Diamond syndrome 1 • Shwachman-Diamond syndrome 1;Aplastic anemia • Aplastic anemia	Pathogenic (Jul 15, 2023)
7-66995302-C-CA		Aplastic anemia	Likely pathogenic (Aug 28, 2023)
7-66995310-G-A		not specified	Likely benign (Mar 10, 2017)
7-66995310-GA-G		Aplastic anemia	Pathogenic (Oct 19, 2023)
7-66995311-A-G		not specified • SBDS-related disorder	Uncertain significance (Dec 26, 2023)
7-66995316-G-GT		Shwachman-Diamond syndrome 1	Pathogenic (Mar 01, 2004)
7-66995317-T-A		Aplastic anemia	Likely pathogenic (Feb 10, 2023)
7-66995320-T-G		Shwachman-Diamond syndrome 1 • Aplastic anemia	Pathogenic/Likely pathogenic (Apr 10, 2023)
7-66995323-T-C		Aplastic anemia	Likely pathogenic (Jul 28, 2023)
7-66995348-C-T		Inborn genetic diseases	Uncertain significance (Jun 08, 2022)
7-66995357-T-A			Likely pathogenic (Nov 30, 2018)
7-66995361-C-CCGTA		Inborn genetic diseases	Pathogenic (Jul 27, 2021)
7-66995377-T-C			Likely pathogenic (May 19, 2015)
7-66995378-T-A		Inborn genetic diseases	Uncertain significance (May 05, 2015)
7-66995380-G-A		Shwachman-Diamond syndrome 1	Uncertain significance (-)
7-66995382-T-C		Inborn genetic diseases	Likely benign (Nov 19, 2020)
7-66995394-G-T		Shwachman-Diamond syndrome 1	Uncertain significance (Apr 16, 2018)
7-66995394-G-GT			Likely pathogenic (May 18, 2017)
7-66995399-TG-T		Shwachman-Diamond syndrome 1 • Aplastic anemia	Pathogenic (Jul 20, 2023)
7-66995404-GT-G		Shwachman-Diamond syndrome 1 • Aplastic anemia	Pathogenic (Oct 12, 2023)
7-66995433-A-T			Benign (Mar 03, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYW1	protein_coding	protein_coding	ENST00000359626	16	244342

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.96e-10	0.998	125674	0	73	125747	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.978	358	414	0.865	0.0000226	4874
Missense in Polyphen		120	133.96	0.89581		1480
Synonymous	0.906	144	159	0.908	0.0000103	1285
Loss of Function	2.85	23	43.2	0.532	0.00000223	490

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000383	0.000382
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000389	0.000387
Middle Eastern	0.000109	0.000109
South Asian	0.000428	0.000425
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the condensation of N- methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate in wybutosine biosynthesis (By similarity). {ECO:0000250}.
• Pathway: Synthesis of wybutosine at G37 of tRNA(Phe);tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA;wybutosine biosynthesis;7-(3-amino-3-carboxypropyl)-wyosine biosynthesis (Consensus)

Recessive Scores

• pRec: 0.0869

Intolerance Scores

• loftool: 0.513
• rvis_EVS: -1.17
• rvis_percentile_EVS: 5.99

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.332
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.622

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tyw1

Gene ontology

• Biological process: tRNA processing;oxidation-reduction process
• Molecular function: FMN binding;metal ion binding;4 iron, 4 sulfur cluster binding;tRNA-4-demethylwyosine synthase activity