TSFM

Ts translation elongation factor, mitochondrial

Basic information

Region (hg38): 12:57782760-57808071

Links

ENSG00000123297 ∙ NCBI:10102 ∙ OMIM:604723 ∙ HGNC:12367 ∙ Uniprot:P43897 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR
• fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 3	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; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	17033963; 21119709; 22499341

ClinVar

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

• not provided (380 variants)
• Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (93 variants)
• Inborn genetic diseases (28 variants)
• not specified (12 variants)
• Nephrotic syndrome, type 21 (2 variants)
• See cases (2 variants)
• Encephalomyopathy with respiratory failure and lactic acidosis (2 variants)
• Combined oxidative phosphorylation deficiency (1 variants)
• Primary dilated cardiomyopathy (1 variants)
• Steroid-resistant nephrotic syndrome (1 variants)
• Skeletal myopathy (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSFM 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			3	127	3	133
missense	1	3	117	3	4	128
nonsense	8	11	1			20
start loss			5			5
frameshift	11	16	1			28
inframe indel			1			1
splice donor/acceptor (+/-2bp)		8				8
splice region			3	29		32
non coding			24	37	13	74
Total	20	38	152	167	20

Highest pathogenic variant AF is 0.0000329

Variants in TSFM

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

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

Position	Type	Phenotype	Significance	ClinVar
12-57782794-C-A		not specified	Likely benign (Dec 03, 2015)
12-57782802-A-G			Uncertain significance (Feb 04, 2022)
12-57782802-A-T			Uncertain significance (Jul 06, 2022)
12-57782803-T-C			Uncertain significance (May 23, 2023)
12-57782803-T-G		Skeletal myopathy	Uncertain significance (Oct 12, 2015)
12-57782804-G-A			Uncertain significance (May 29, 2021)
12-57782803-T-TGTCGCTGCTGCG			Uncertain significance (Jun 22, 2022)
12-57782806-C-A		Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3	Pathogenic/Likely pathogenic (Jul 29, 2023)
12-57782806-C-T		Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3	Benign (Jan 30, 2024)
12-57782807-G-C			Likely benign (Dec 09, 2023)
12-57782808-C-T			Likely benign (Nov 03, 2023)
12-57782810-G-A			Likely benign (Mar 09, 2022)
12-57782810-G-T			Likely benign (Jul 10, 2023)
12-57782811-C-T		Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3	Likely benign (Jan 05, 2024)
12-57782812-T-C			Uncertain significance (Jan 07, 2022)
12-57782813-G-A			Likely benign (Dec 01, 2023)
12-57782813-G-T		Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3	Likely benign (Jan 22, 2024)
12-57782814-C-A			Likely benign (Oct 22, 2023)
12-57782818-C-A			Pathogenic (Jan 15, 2022)
12-57782818-C-G			Uncertain significance (Jun 07, 2022)
12-57782818-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
12-57782820-C-T			Likely benign (Sep 29, 2021)
12-57782822-G-T			Likely benign (Nov 12, 2023)
12-57782823-C-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2022)
12-57782824-G-C			Uncertain significance (Jun 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSFM	protein_coding	protein_coding	ENST00000323833	7	25483

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.92e-9	0.132	125214	0	394	125608	0.00157

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	177	169	1.05	0.00000829	2167
Missense in Polyphen		59	63.488	0.92931		787
Synonymous	-0.518	77	71.4	1.08	0.00000368	712
Loss of Function	0.247	14	15.0	0.931	7.26e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000643	0.000639
Ashkenazi Jewish	0.000200	0.000199
East Asian	0.000164	0.000163
Finnish	0.0145	0.0138
European (Non-Finnish)	0.000643	0.000599
Middle Eastern	0.000164	0.000163
South Asian	0.00	0.00
Other	0.00124	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF- Tu.GTP complex up to the GTP hydrolysis stage on the ribosome. {ECO:0000255|HAMAP-Rule:MF_03135, ECO:0000269|PubMed:27677415}.
• Pathway: Translation;Metabolism of proteins;Mitochondrial translation elongation;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.199

Intolerance Scores

• loftool: 0.376
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.394
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.513

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tsfm
• 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); pigmentation phenotype; vision/eye phenotype

Gene ontology

• Biological process: translational elongation;regulation of DNA-templated transcription, elongation;mitochondrial translational elongation;regulation of mitochondrial translation
• Cellular component: nucleus;mitochondrion;mitochondrial matrix
• Molecular function: RNA binding;translation elongation factor activity;protein binding