TSFM

Ts translation elongation factor, mitochondrial

Basic information

Region (hg38): 12:57782761-57808071

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 (452 variants)
Fatal_mitochondrial_disease_due_to_combined_oxidative_phosphorylation_defect_type_3 (109 variants)
Inborn_genetic_diseases (45 variants)
not_specified (14 variants)
TSFM-related_disorder (11 variants)
See_cases (2 variants)
Encephalomyopathy_with_respiratory_failure_and_lactic_acidosis (2 variants)
Primary_dilated_cardiomyopathy (1 variants)
Combined_oxidative_phosphorylation_deficiency (1 variants)
Nephrotic_syndrome,_type_21 (1 variants)
Skeletal_myopathy (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. These statistics are base on transcript: NM_000005726.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	166 clinvar	1 clinvar	172
missense	1 clinvar	8 clinvar	142 clinvar	8 clinvar	1 clinvar	160
nonsense	8 clinvar	13 clinvar	1 clinvar			22
start loss		3	3			6
frameshift	18 clinvar	20 clinvar	1 clinvar			39
splice donor/acceptor (+/-2bp)		11 clinvar				11
Total	27	55	152	174	2

Highest pathogenic variant AF is 0.0006877717

Loading clinvar variants...

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