TBC1D7

TBC1 domain family member 7, the group of TSC complex

Basic information

Region (hg38): 6:13266542-13328583

Links

ENSG00000145979 ∙ NCBI:51256 ∙ OMIM:612655 ∙ HGNC:21066 ∙ Uniprot:Q9P0N9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrocephaly/megalencephaly syndrome, autosomal recessive (Moderate), mode of inheritance: AR
• macrocephaly/megalencephaly syndrome, autosomal recessive (Limited), mode of inheritance: AR
• macrocephaly/megalencephaly syndrome, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Macrocephaly/megalencephaly syndrome, autosomal recessive	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	Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	23687350; 24515783

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBC1D7 gene.

• not provided (2 variants)
• Macrocephaly/megalencephaly syndrome, autosomal recessive (1 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBC1D7 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	15	4	20
missense			36	5	3	44
nonsense	1		1			2
start loss						0
frameshift	2	1	1			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1		2	3
non coding				14	21	35
Total	3	2	39	34	28

Highest pathogenic variant AF is 0.0000263

Variants in TBC1D7

This is a list of pathogenic ClinVar variants found in the TBC1D7 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-13272855-C-T		PHACTR1-related disorder	Likely benign (May 23, 2022)
6-13272856-G-A			Benign (Jul 01, 2024)
6-13272859-GGCGGCTGAGCCAGAGGCCAACTGCAGAGGAACTGGAACAGAGGAACATTTTGAAAC-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Dec 13, 2019)
6-13272864-C-A		Developmental and epileptic encephalopathy, 70	Pathogenic (May 18, 2021)
6-13272904-A-T		Developmental and epileptic encephalopathy, 70	Pathogenic (Nov 25, 2020)
6-13278257-AT-A		PHACTR1-related disorder	Likely benign (Jul 10, 2019)
6-13278271-G-A		PHACTR1-related disorder	Uncertain significance (Feb 05, 2024)
6-13278274-A-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Feb 02, 2022)
6-13278319-T-C		Developmental and epileptic encephalopathy, 70	Pathogenic (Jul 17, 2023)
6-13281154-ACT-A			Benign (Jun 01, 2022)
6-13283415-CCTGCAGCTCAGTCAAAGGCCCACGGT-C		PHACTR1-related disorder	Uncertain significance (Apr 24, 2024)
6-13283467-C-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Oct 09, 2024)
6-13283473-C-T		Developmental and epileptic encephalopathy, 70 • not specified	Uncertain significance (May 04, 2022)
6-13283535-G-A		PHACTR1-related disorder	Likely benign (Aug 01, 2019)
6-13283538-G-T		not specified	Uncertain significance (Jun 22, 2021)
6-13283548-A-T			Likely benign (Apr 01, 2024)
6-13283555-C-G		Developmental and epileptic encephalopathy, 70	Uncertain significance (Nov 02, 2023)
6-13286183-C-G		not specified	Uncertain significance (Aug 28, 2023)
6-13286208-T-G			Uncertain significance (Sep 13, 2022)
6-13286236-G-GT			Likely benign (Dec 01, 2023)
6-13287083-C-T		PHACTR1-related disorder	Benign (May 28, 2019)
6-13305105-C-A		not specified	Uncertain significance (Jun 01, 2023)
6-13305105-C-T		not specified	Uncertain significance (Nov 10, 2024)
6-13305109-A-C		not specified	Uncertain significance (Jan 26, 2023)
6-13305113-G-C			Benign (Jan 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBC1D7	protein_coding	protein_coding	ENST00000606214	7	62042

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.94e-12	0.0217	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.144	168	173	0.969	0.0000102	1924
Missense in Polyphen		39	58.126	0.67095		695
Synonymous	-0.382	67	63.1	1.06	0.00000382	537
Loss of Function	-0.291	17	15.8	1.08	8.17e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000172	0.000109
Finnish	0.000192	0.000185
European (Non-Finnish)	0.000268	0.000264
Middle Eastern	0.000172	0.000109
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question. {ECO:0000269|PubMed:22795129}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Rab regulation of trafficking (Consensus)

Intolerance Scores

• loftool: 0.978
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.486
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbc1d7

Gene ontology

• Biological process: positive regulation of protein ubiquitination;negative regulation of TOR signaling;positive regulation of GTPase activity;response to growth factor;activation of GTPase activity;negative regulation of cilium assembly
• Cellular component: cytosol;cytoplasmic vesicle;ciliary basal body
• Molecular function: GTPase activator activity;protein binding;Rab GTPase binding