ASCC3

activating signal cointegrator 1 complex subunit 3, the group of RNA helicases|DNA helicases|Activating signal cointegrator 1 complex

Basic information

Region (hg38): 6:100508193-100881372

Previous symbols: [ "HELIC1" ]

Links

ENSG00000112249 ∙ NCBI:10973 ∙ OMIM:614217 ∙ HGNC:18697 ∙ Uniprot:Q8N3C0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASCC3 gene.

• Inborn genetic diseases (76 variants)
• not provided (26 variants)
• not specified (4 variants)
• INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 81 (4 variants)
• ASCC3-related disorder (2 variants)
• Congenital myopathy (2 variants)
• ASCC3-associated disorder (2 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASCC3 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	5	8
missense			85	5	3	93
nonsense		2				2
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1	2			3
splice region					1	1
non coding					1	1
Total	0	3	91	8	9

Highest pathogenic variant AF is 0.0000593

Variants in ASCC3

This is a list of pathogenic ClinVar variants found in the ASCC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-100509405-G-A			Uncertain significance (Apr 01, 2024)
6-100509460-C-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
6-100509947-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
6-100509972-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
6-100510010-A-G		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
6-100510092-A-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
6-100512714-G-A		Inborn genetic diseases	Likely benign (Nov 17, 2023)
6-100512720-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
6-100512904-T-G			Uncertain significance (Aug 07, 2018)
6-100516230-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
6-100516234-G-C		Inborn genetic diseases	Likely benign (May 24, 2023)
6-100516259-A-G		ASCC3-associated disorder • Intellectual developmental disorder, autosomal recessive 81	Uncertain significance (Dec 05, 2023)
6-100516316-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
6-100518018-A-G		Inborn genetic diseases	Uncertain significance (Dec 07, 2023)
6-100518030-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
6-100518061-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
6-100518084-T-C		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
6-100540167-CAT-C		Intellectual developmental disorder, autosomal recessive 81	Pathogenic (Mar 05, 2024)
6-100540245-T-C		See cases • Intellectual developmental disorder, autosomal recessive 81	Uncertain significance (Jan 29, 2019)
6-100540326-A-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
6-100540374-T-TA			Uncertain significance (Mar 30, 2023)
6-100589638-A-G		Inborn genetic diseases	Uncertain significance (Apr 26, 2023)
6-100589672-G-A		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
6-100589728-G-A		Inborn genetic diseases	Uncertain significance (May 10, 2022)
6-100589734-C-T		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASCC3	protein_coding	protein_coding	ENST00000369162	41	373179

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-20	1.00	125464	0	284	125748	0.00113

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.23	938	1.15e+3	0.815	0.0000587	14534
Missense in Polyphen		268	433.44	0.61831		5255
Synonymous	-0.371	402	393	1.02	0.0000192	4154
Loss of Function	5.58	55	121	0.453	0.00000739	1391

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00457	0.00457
Ashkenazi Jewish	0.00	0.00
East Asian	0.00136	0.00136
Finnish	0.00273	0.00273
European (Non-Finnish)	0.000836	0.000809
Middle Eastern	0.00136	0.00136
South Asian	0.000431	0.000425
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-5' DNA helicase involved in repair of alkylated DNA. Promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3- methylcytosine (3mC) within double-stranded regions (PubMed:22055184). Part of the ASC-1 complex that enhances NF- kappa-B, SRF and AP1 transactivation (PubMed:12077347). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:22055184}.
• Pathway: Mesodermal Commitment Pathway;DNA Repair;ALKBH3 mediated reversal of alkylation damage;Reversal of alkylation damage by DNA dioxygenases;DNA Damage Reversal (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.780
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.21

Haploinsufficiency Scores

• pHI: 0.376
• hipred: Y
• hipred_score: 0.706
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ascc3
• Phenotype: homeostasis/metabolism phenotype; skeleton phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: DNA dealkylation involved in DNA repair;cell population proliferation;DNA duplex unwinding
• Cellular component: nucleus;nucleoplasm;cytosol;membrane;nuclear speck;activating signal cointegrator 1 complex
• Molecular function: RNA binding;protein binding;ATP binding;ATP-dependent helicase activity;ATP-dependent 3'-5' DNA helicase activity