VPS13C

vacuolar protein sorting 13 homolog C, the group of bridge-like lipid transfer protein family

Basic information

Region (hg38): 15:61852389-62060473

Links

ENSG00000129003 ∙ NCBI:54832 ∙ OMIM:608879 ∙ HGNC:23594 ∙ Uniprot:Q709C8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal recessive early-onset Parkinson disease 23 (Moderate), mode of inheritance: AR
• young-onset Parkinson disease (Supportive), mode of inheritance: AR
• autosomal recessive early-onset Parkinson disease 23 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 23, autosomal recessive, early onset	AR	Neurologic	Individuals have been described with levodopa response	Neurologic	26942284

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS13C gene.

• not provided (11 variants)
• Autosomal recessive early-onset Parkinson disease 23 (6 variants)
• Parkinson disease (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS13C 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	147	29	179
missense		1	298	33	26	358
nonsense	8	13	11			32
start loss						0
frameshift	9	4	7			20
inframe indel						0
splice donor/acceptor (+/-2bp)	1	9	6	1		17
splice region			10	34	7	51
non coding			6	91	155	252
Total	18	27	331	272	210

Highest pathogenic variant AF is 0.0000132

Variants in VPS13C

This is a list of pathogenic ClinVar variants found in the VPS13C region.

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

Position	Type	Phenotype	Significance	ClinVar
15-61854399-C-T			Benign (May 20, 2021)
15-61854469-T-C			Benign (Mar 22, 2023)
15-61854478-G-C			Likely benign (Nov 22, 2023)
15-61854490-T-G			Likely benign (Jan 19, 2024)
15-61854507-A-G			Likely benign (Apr 30, 2022)
15-61854523-C-T			Likely benign (Apr 24, 2023)
15-61854543-T-C			Benign/Likely benign (Aug 01, 2024)
15-61854545-G-T			Uncertain significance (Nov 17, 2021)
15-61854770-T-A			Benign (May 16, 2021)
15-61854857-T-G			Likely benign (Jun 12, 2022)
15-61854884-G-T			Uncertain significance (Nov 17, 2022)
15-61854888-C-A			Conflicting classifications of pathogenicity (Feb 22, 2023)
15-61854904-T-G			Likely benign (Nov 13, 2021)
15-61854917-T-C			Uncertain significance (May 09, 2022)
15-61854919-A-T		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
15-61854947-C-T			Likely benign (Jan 19, 2024)
15-61854971-A-G			Benign (Dec 22, 2023)
15-61855008-T-A			Benign (May 16, 2021)
15-61856283-T-C			Uncertain significance (Mar 25, 2022)
15-61856297-T-C			Uncertain significance (Aug 05, 2021)
15-61856305-A-G			Uncertain significance (Nov 23, 2021)
15-61856316-G-A			Likely benign (Aug 03, 2021)
15-61856331-T-C			Likely benign (May 22, 2022)
15-61856365-C-T			Uncertain significance (Dec 21, 2021)
15-61856381-T-G			Likely benign (Jul 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS13C	protein_coding	protein_coding	ENST00000261517	85	208085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.65e-49	1.00	124995	0	753	125748	0.00300

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.29	1994	1.84e+3	1.08	0.0000903	24642
Missense in Polyphen		575	583.44	0.98553		7973
Synonymous	-2.53	722	640	1.13	0.0000316	6963
Loss of Function	5.40	110	190	0.578	0.00000964	2546

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00369	0.00362
Ashkenazi Jewish	0.00110	0.00109
East Asian	0.000744	0.000707
Finnish	0.0110	0.0108
European (Non-Finnish)	0.00319	0.00307
Middle Eastern	0.000744	0.000707
South Asian	0.00167	0.00154
Other	0.00268	0.00245

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential. Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization. {ECO:0000269|PubMed:26942284}.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.971
• rvis_EVS: -0.81
• rvis_percentile_EVS: 12.08

Haploinsufficiency Scores

• pHI: 0.211
• hipred: N
• hipred_score: 0.466
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.449

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps13c
• Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: protein targeting to vacuole;Golgi to endosome transport;mitochondrion organization;protein retention in Golgi apparatus;negative regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization
• Cellular component: cytoplasm;mitochondrial outer membrane;cytosol;extrinsic component of membrane;extracellular exosome