SMARCAD1

SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1

Basic information

Region (hg38): 4:94207611-94291292

Links

ENSG00000163104 ∙ NCBI:56916 ∙ OMIM:612761 ∙ HGNC:18398 ∙ Uniprot:Q9H4L7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated congenital adermatoglyphia (Strong), mode of inheritance: AD
• absence of fingerprints-congenital milia syndrome (Supportive), mode of inheritance: AD
• palmoplantar keratoderma-sclerodactyly syndrome (Supportive), mode of inheritance: AD
• isolated congenital adermatoglyphia (Supportive), mode of inheritance: AD
• ectodermal dysplasia syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Huriez syndrome	AD	Oncologic	Huriez syndrome has been described as involving significant risk of aggressive squamous cell skin carcinoma, and awareness may allow surveillance and early management of disease	Dermatologic; Oncologic	4298032; 8731679; 10631162; 20619487; 21820097; 24664640; 24909267; 26932190; 29409814

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCAD1 gene.

• Adermatoglyphia (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCAD1 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				5	4	9
missense	1		34	2	5	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		3	4
non coding	1	1			10	12
Total	2	1	34	7	19

Highest pathogenic variant AF is 0.0000131

Variants in SMARCAD1

This is a list of pathogenic ClinVar variants found in the SMARCAD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-94208087-T-C			Benign (Nov 12, 2018)
4-94208407-A-G		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
4-94208431-A-G		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
4-94208483-C-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
4-94208506-C-G		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
4-94208520-G-C		Inborn genetic diseases	Uncertain significance (May 09, 2024)
4-94208536-G-A		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
4-94208874-G-A			Benign (Nov 12, 2018)
4-94225904-C-G			Benign (Nov 12, 2018)
4-94226161-C-A		Inborn genetic diseases	Uncertain significance (May 30, 2024)
4-94226232-G-A		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 15, 2024)
4-94226247-T-C		Inborn genetic diseases	Uncertain significance (Jan 06, 2023)
4-94226251-A-G		Inborn genetic diseases	Likely benign (Dec 28, 2023)
4-94226402-C-T			Benign (Jun 19, 2021)
4-94233970-G-A		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
4-94233997-A-G			Benign (Mar 29, 2018)
4-94234036-C-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
4-94236985-A-G		Inborn genetic diseases	Uncertain significance (Apr 08, 2024)
4-94237008-T-C		SMARCAD1-related disorder	Likely benign (Feb 21, 2019)
4-94240845-C-T			Benign (Nov 12, 2018)
4-94240951-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
4-94241274-G-A			Benign (Nov 12, 2018)
4-94249688-G-A		Basan syndrome • Keratoderma with scleroatrophy of the extremities • Adermatoglyphia	Benign (Jul 15, 2021)
4-94250771-A-G		Inborn genetic diseases	Uncertain significance (May 20, 2024)
4-94252619-T-C		Inborn genetic diseases	Uncertain significance (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCAD1	protein_coding	protein_coding	ENST00000359052	23	83682

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.37e-9	125659	0	2	125661	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.49	304	530	0.573	0.0000259	6877
Missense in Polyphen		34	150.29	0.22623		1874
Synonymous	-0.643	191	180	1.06	0.00000882	1797
Loss of Function	6.90	1	57.4	0.0174	0.00000291	717

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000579	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000579	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.
• Disease: DISEASE: Basan syndrome (BSNS) [MIM:129200]: An autosomal dominant form of adermatoglyphia associated with congenital facial milia, acral blistering, digital contractures, and nail abnormalities. Adermatoglyphia is defined by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints. {ECO:0000269|PubMed:24664640, ECO:0000269|PubMed:26932190}. Note=The disease is caused by mutations affecting the gene represented in this entry. Splice site mutations causing aberrant splicing of skin-specific isoform 3 are likely to exert a loss-of- function effect and are involved in BSNS. {ECO:0000269|PubMed:24664640, ECO:0000269|PubMed:26932190}.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.0130
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.58

Haploinsufficiency Scores

• pHI: 0.319
• hipred: Y
• hipred_score: 0.853
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcad1
• Phenotype: growth/size/body region phenotype; cellular phenotype; digestive/alimentary phenotype; reproductive 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); normal 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); skeleton phenotype

Gene ontology

• Biological process: regulation of DNA recombination;DNA double-strand break processing;chromatin organization;chromatin remodeling;nucleotide metabolic process;ATP-dependent chromatin remodeling;positive regulation of transcription, DNA-templated;protein homooligomerization;chromosome separation;histone H3 deacetylation;histone H4 deacetylation
• Cellular component: heterochromatin;nucleoplasm;nuclear matrix;site of double-strand break;nuclear replication fork
• Molecular function: nucleic acid binding;DNA binding;helicase activity;protein binding;ATP binding