ASCC1

activating signal cointegrator 1 complex subunit 1, the group of Activating signal cointegrator 1 complex

Basic information

Region (hg38): 10:72096031-72217134

Links

ENSG00000138303 ∙ NCBI:51008 ∙ OMIM:614215 ∙ HGNC:24268 ∙ Uniprot:Q8N9N2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinal muscular atrophy with congenital bone fractures 2 (Definitive), mode of inheritance: AR
• spinal muscular atrophy with congenital bone fractures 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Barrett esophagus/Esophageal adenocarcinoma	AD	Gastrointestinal; Oncologic	Awareness of disease risk may allow surveillance, preventive measures (eg, related to Barrett esophagus) and early treatment of malignancy, which may reduce morbidity and mortality	Gastrointestinal; Musculoskeletal; Neurologic; Oncologic	21791690; 26924529; 28218388; 30327447

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASCC1 gene.

• not provided (129 variants)
• Spinal muscular atrophy with congenital bone fractures 2 (13 variants)
• Inborn genetic diseases (12 variants)
• Barrett esophagus (2 variants)
• Fetal akinesia deformation sequence 1 (1 variants)
• Barrett esophagus/esophageal adenocarcinoma (1 variants)
• not specified (1 variants)
• Fetal akinesia deformation sequence 1;Arthrogryposis multiplex congenita (1 variants)
• See cases (1 variants)
• ASCC1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASCC1 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	2	18
missense			35	5	3	43
nonsense	8	1	1			10
start loss						0
frameshift	2	2				4
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			3	3		6
non coding	1		1	33	23	58
Total	12	6	38	53	28

Highest pathogenic variant AF is 0.0000592

Variants in ASCC1

This is a list of pathogenic ClinVar variants found in the ASCC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-72097226-A-G			Benign (May 10, 2021)
10-72097356-C-G			Uncertain significance (Jul 01, 2022)
10-72097363-C-T			Uncertain significance (Jan 02, 2024)
10-72097364-G-A			Benign (Jan 21, 2024)
10-72097385-G-A			Benign (Jul 31, 2023)
10-72097387-T-C		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
10-72097391-C-T			Likely benign (Dec 31, 2022)
10-72097398-G-C			Uncertain significance (Jul 05, 2022)
10-72097404-T-C		Inborn genetic diseases	Uncertain significance (Aug 03, 2022)
10-72097408-T-C			Uncertain significance (Nov 16, 2021)
10-72097428-C-A		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
10-72097434-T-C		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
10-72097448-C-A			Uncertain significance (Jun 30, 2022)
10-72097458-G-A			Likely benign (Mar 03, 2022)
10-72102274-C-T			Benign (May 10, 2021)
10-72102365-G-A		ASCC1-related disorder	Likely benign (Nov 23, 2020)
10-72102392-G-C			Likely benign (May 15, 2019)
10-72102416-T-C			Likely benign (Jul 14, 2023)
10-72102424-T-C			Likely benign (Aug 17, 2023)
10-72102428-G-C			Likely benign (Oct 06, 2022)
10-72102843-C-T			Likely benign (Nov 01, 2022)
10-72102844-G-A			Likely benign (Oct 17, 2023)
10-72102866-T-A			Likely benign (Aug 11, 2022)
10-72102868-G-A			Likely benign (May 10, 2018)
10-72102872-G-A			Likely benign (Nov 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASCC1	protein_coding	protein_coding	ENST00000342444	11	120615

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.61e-14	0.0354	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.838	173	207	0.836	0.0000107	2643
Missense in Polyphen		42	58.997	0.7119		722
Synonymous	-0.146	75	73.4	1.02	0.00000378	729
Loss of Function	0.352	22	23.9	0.922	0.00000140	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000749	0.000749
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in DNA damage repair as component of the ASCC complex (PubMed:29997253). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). In cells responding to gastrin-activated paracrine signals, it is involved in the induction of SERPINB2 expression by gastrin. May also play a role in the development of neuromuscular junction. {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:19074642, ECO:0000269|PubMed:26924529, ECO:0000269|PubMed:29997253}.
• Disease: DISEASE: Spinal muscular atrophy with congenital bone fractures 2 (SMABF2) [MIM:616867]: An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures. {ECO:0000269|PubMed:26924529}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA Repair;ALKBH3 mediated reversal of alkylation damage;Reversal of alkylation damage by DNA dioxygenases;DNA Damage Reversal (Consensus)

Recessive Scores

• pRec: 0.0761

Intolerance Scores

• rvis_EVS: 0.8
• rvis_percentile_EVS: 87.49

Haploinsufficiency Scores

• pHI: 0.0667
• hipred: N
• hipred_score: 0.144
• ghis: 0.431

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.912

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ascc1

Zebrafish Information Network

• Gene name: ascc1
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: DNA dealkylation involved in DNA repair;regulation of transcription, DNA-templated
• Cellular component: nucleus;nucleoplasm;transcription factor complex;nuclear speck;neuromuscular junction
• Molecular function: RNA binding;protein binding