SMARCC1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1, the group of BAF complex|GBAF complex|PBAF complex|Myb/SANT domain containing|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 3:47585269-47782106

Links

ENSG00000173473 ∙ NCBI:6599 ∙ OMIM:601732 ∙ HGNC:11104 ∙ Uniprot:Q92922 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hydrocephalus, congenital, 5, susceptibility to (Strong), mode of inheritance: AD
• SMARCC1-associated developmental dysgenesis syndrome (Definitive), mode of inheritance: AD
• hydrocephalus, congenital, 5, susceptibility to (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hydrocephalus, congenital, 5, susceptibility to	AD	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	Neurologic	29983323; 33077954

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCC1 gene.

• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCC1 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	1	2
missense			67	3		70
nonsense	1	1	2			4
start loss						0
frameshift			8			8
inframe indel		1				1
splice donor/acceptor (+/-2bp)			2			2
splice region				1		1
non coding						0
Total	1	2	79	4	1

Variants in SMARCC1

This is a list of pathogenic ClinVar variants found in the SMARCC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-47588265-C-T		Inborn genetic diseases	Likely benign (Jul 27, 2024)
3-47588267-G-A		Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
3-47588291-T-C		Inborn genetic diseases	Uncertain significance (May 11, 2022)
3-47588303-G-T			Uncertain significance (Jul 20, 2021)
3-47590670-T-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
3-47590758-G-A		SMARCC1-related disorder	Likely benign (Aug 12, 2024)
3-47590772-C-G		Inborn genetic diseases	Uncertain significance (May 17, 2023)
3-47590786-C-T			Uncertain significance (Jul 20, 2021)
3-47590816-G-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
3-47590821-TG-T			Uncertain significance (Mar 01, 2022)
3-47610096-G-A		SMARCC1-associated developmental dysgenesis syndrome	Uncertain significance (Jun 10, 2021)
3-47610139-C-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
3-47610186-C-CT		SMARCC1-related disorder	Uncertain significance (Sep 08, 2022)
3-47610225-G-C		Inborn genetic diseases	Uncertain significance (Nov 13, 2023)
3-47610263-T-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
3-47610279-T-C		Inborn genetic diseases	Uncertain significance (Oct 07, 2024)
3-47610282-G-A		Inborn genetic diseases	Uncertain significance (May 10, 2022)
3-47610335-C-G		SMARCC1-related disorder	Likely benign (Feb 09, 2024)
3-47622204-T-TA			Uncertain significance (Oct 26, 2023)
3-47622221-T-C		SMARCC1-related disorder	Uncertain significance (May 15, 2023)
3-47622234-T-G			Uncertain significance (Feb 24, 2022)
3-47622292-AAGA-G		Global developmental delay	Likely pathogenic (Oct 25, 2021)
3-47622304-A-G			Uncertain significance (Jun 25, 2024)
3-47622313-ATCTT-A			Uncertain significance (Dec 14, 2022)
3-47622315-CT-C		Congenital hydrocephalus • Hydrocephalus, congenital, 5, susceptibility to	Likely pathogenic; risk factor (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCC1	protein_coding	protein_coding	ENST00000254480	28	196835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.70e-9	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	438	608	0.721	0.0000320	7242
Missense in Polyphen		78	174.42	0.44719		2095
Synonymous	0.238	212	216	0.979	0.0000118	2091
Loss of Function	7.23	3	66.7	0.0450	0.00000364	765

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.0000576	0.0000544
Finnish	0.0000489	0.0000462
European (Non-Finnish)	0.0000557	0.0000527
Middle Eastern	0.0000576	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. May stimulate the ATPase activity of the catalytic subunit of the complex (PubMed:10078207, PubMed:29374058). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron- specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:P97496, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:11018012, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;the information processing pathway at the ifn beta enhancer;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Glucocorticoid receptor regulatory network;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;TNFalpha;Transcriptional regulation by RUNX1;Regulation of Androgen receptor activity (Consensus)

Intolerance Scores

• loftool: 0.186
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.28

Haploinsufficiency Scores

• pHI: 0.822
• hipred: Y
• hipred_score: 0.831
• ghis: 0.629

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcc1
• Phenotype: cellular phenotype; hematopoietic system 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; embryo phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: smarcc1a
• Affected structure: heart
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;nervous system development;insulin receptor signaling pathway;animal organ morphogenesis;prostate gland development;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;ATP-dependent chromatin remodeling;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin;XY body;nucleus;nucleoplasm;cytoplasm;SWI/SNF complex;protein-containing complex;npBAF complex;nBAF complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator activity;protein binding;nucleosomal DNA binding;protein N-terminus binding