SMARCD1

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1, the group of BAF complex|GBAF complex|PBAF complex

Basic information

Region (hg38): 12:50085199-50100707

Links

ENSG00000066117 ∙ NCBI:6602 ∙ OMIM:601735 ∙ HGNC:11106 ∙ Uniprot:Q96GM5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 15 (Strong), mode of inheritance: AD
• Coffin-Siris syndrome (Supportive), mode of inheritance: AD
• Coffin-Siris syndrome 11 (Moderate), mode of inheritance: AD
• Coffin-Siris syndrome 11 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coffin-Siris syndrome 11	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	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	30879640

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCD1 gene.

• not provided (38 variants)
• Coffin-Siris syndrome 11 (9 variants)
• Inborn genetic diseases (8 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCD1 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				2		2
missense			34	1	1	36
nonsense	1					1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding					8	8
Total	1	0	36	3	9

Variants in SMARCD1

This is a list of pathogenic ClinVar variants found in the SMARCD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-50085458-C-T			Uncertain significance (Aug 01, 2023)
12-50085476-C-T		Coffin-Siris syndrome 11 • Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
12-50085479-C-T			Uncertain significance (Oct 24, 2022)
12-50085499-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
12-50085511-C-G		Coffin-Siris syndrome 11 • Inborn genetic diseases	Uncertain significance (Mar 30, 2022)
12-50085517-C-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2020)
12-50085527-T-C			Uncertain significance (Dec 04, 2022)
12-50085536-C-G			Uncertain significance (May 03, 2021)
12-50085546-G-A			Likely benign (Apr 02, 2021)
12-50086152-C-T		Coffin-Siris syndrome 11	Benign (Jul 15, 2021)
12-50086156-T-G			Uncertain significance (May 04, 2022)
12-50086183-G-T		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
12-50086186-G-A		Coffin-Siris syndrome 11	Likely benign (Mar 31, 2022)
12-50086236-C-T		Coffin-Siris syndrome 11	Uncertain significance (Jul 25, 2023)
12-50086282-G-T			Uncertain significance (Feb 01, 2023)
12-50086319-G-T		Coffin-Siris syndrome 11	Benign/Likely benign (Dec 01, 2023)
12-50086327-C-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
12-50086348-A-G			Uncertain significance (Oct 18, 2022)
12-50086481-G-GGTGGTGGTA			Benign (Jun 01, 2021)
12-50086502-A-G			Benign (May 23, 2021)
12-50086783-G-A		Inborn genetic diseases	Uncertain significance (Apr 21, 2022)
12-50086795-C-CT			Uncertain significance (Apr 03, 2023)
12-50086797-CTT-C			Uncertain significance (Feb 16, 2022)
12-50086841-G-A		Global developmental delay	Conflicting classifications of pathogenicity (Nov 10, 2022)
12-50086850-T-C			Uncertain significance (Feb 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCD1	protein_coding	protein_coding	ENST00000394963	13	15741

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000532	125739	0	3	125742	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.44	117	279	0.420	0.0000163	3337
Missense in Polyphen		16	63.732	0.25105		762
Synonymous	0.903	88	99.5	0.885	0.00000512	1025
Loss of Function	4.78	2	30.5	0.0655	0.00000176	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000635	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
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 (PubMed:8804307, 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). Has a strong influence on vitamin D-mediated transcriptional activity from an enhancer vitamin D receptor element (VDRE). May be a link between mammalian SWI-SNF-like chromatin remodeling complexes and the vitamin D receptor (VDR) heterodimer (PubMed:14698202). Mediates critical interactions between nuclear receptors and the BRG1/SMARCA4 chromatin-remodeling complex for transactivation (PubMed:12917342). {ECO:0000250|UniProtKB:Q61466, ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:14698202, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:8804307, 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;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.0491
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.983
• hipred: Y
• hipred_score: 0.783
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcd1
• Phenotype: homeostasis/metabolism phenotype; digestive/alimentary phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: smarcd1
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;nervous system development;chromatin-mediated maintenance of transcription;cellular response to fatty acid
• Cellular component: nucleoplasm;SWI/SNF complex;intracellular membrane-bounded organelle;npBAF complex;nBAF complex
• Molecular function: chromatin binding;transcription coactivator activity;signaling receptor binding;protein binding;protein-containing complex scaffold activity