ZSWIM6

zinc finger SWIM-type containing 6, the group of Zinc fingers SWIM-type

Basic information

Region (hg38): 5:61332257-61546172

Links

ENSG00000130449 ∙ NCBI:57688 ∙ OMIM:615951 ∙ HGNC:29316 ∙ Uniprot:Q9HCJ5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acromelic frontonasal dysostosis (Strong), mode of inheritance: AD
• acromelic frontonasal dysostosis (Strong), mode of inheritance: AD
• acromelic frontonasal dysostosis (Supportive), mode of inheritance: AD
• acromelic frontonasal dysostosis (Strong), mode of inheritance: AD
• neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acromelic frontonasal dysostosis; Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features	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; Musculoskeletal; Neurologic	25105228; 29198722

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZSWIM6 gene.

• not provided (616 variants)
• Inborn genetic diseases (52 variants)
• Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (15 variants)
• Acromelic frontonasal dysostosis (10 variants)
• not specified (9 variants)
• ZSWIM6-related condition (7 variants)
• Acromelic frontonasal dysostosis;Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (4 variants)
• See cases (3 variants)
• Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features;Acromelic frontonasal dysostosis (1 variants)
• ZSWIM6 related intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Seizure;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZSWIM6 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			8	172	16	196
missense		2	232	36	16	286
nonsense		1	2			3
start loss						0
frameshift			4			4
inframe indel			24	11	7	42
splice donor/acceptor (+/-2bp)			1			1
splice region			11	11	3	25
non coding			2	51	20	73
Total	0	3	273	270	59

Variants in ZSWIM6

This is a list of pathogenic ClinVar variants found in the ZSWIM6 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-61332267-G-A		ZSWIM6-related disorder	Likely benign (Jul 12, 2019)
5-61332278-G-A			Likely benign (Jul 19, 2022)
5-61332279-G-C			Uncertain significance (Jan 20, 2022)
5-61332285-G-A			Uncertain significance (Aug 12, 2021)
5-61332287-A-G		ZSWIM6-related disorder	Likely benign (Feb 28, 2023)
5-61332293-G-A			Likely benign (Jan 24, 2024)
5-61332294-C-T			Uncertain significance (Jun 27, 2022)
5-61332298-C-T		not specified	Uncertain significance (Jun 01, 2023)
5-61332301-C-A			Conflicting classifications of pathogenicity (Jun 03, 2022)
5-61332303-G-A		Acromelic frontonasal dysostosis	Uncertain significance (Oct 13, 2022)
5-61332312-C-T			Likely benign (Dec 06, 2023)
5-61332326-G-A			Benign (Aug 23, 2022)
5-61332326-GGGC-G		not specified • ZSWIM6-related disorder	Benign/Likely benign (Apr 14, 2023)
5-61332326-GGGCGGC-G		not specified • ZSWIM6-related disorder	Benign/Likely benign (Jan 24, 2024)
5-61332326-GGGCGGCGGC-G			Likely benign (Mar 26, 2021)
5-61332326-GGGCGGCGGCGGCGGCGGCGGGGGCAGCAGC-G		ZSWIM6-related disorder	Benign (Jan 22, 2024)
5-61332326-G-GGGC		ZSWIM6-related disorder	Benign (Jan 29, 2024)
5-61332326-G-GGGCGGC		ZSWIM6-related disorder	Likely benign (Dec 21, 2023)
5-61332326-G-GGGCGGCGGC			Uncertain significance (Mar 19, 2022)
5-61332327-GGCGGCGGCGGCGGCGGCGGGGGCAGCA-G			Benign (Dec 14, 2023)
5-61332330-GGCGGCGGCGGCGGCGGGGGCAGCA-G			Uncertain significance (May 18, 2021)
5-61332333-GGCGGCGGCGGCGGGGGCAGCA-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 25, 2023)
5-61332333-G-GGCGGCGGCGGCGGGGGCAGCA		Inborn genetic diseases	Likely benign (Jan 27, 2023)
5-61332341-C-CGGG		Inborn genetic diseases	Likely benign (Mar 11, 2022)
5-61332341-C-CGGCGGG			Uncertain significance (Sep 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZSWIM6	protein_coding	protein_coding	ENST00000252744	14	213898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.15e-7	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.18	291	572	0.509	0.0000329	7868
Missense in Polyphen		80	229.16	0.34911		2716
Synonymous	1.28	190	214	0.889	0.0000120	2472
Loss of Function	6.17	0	44.3	0.00	0.00000238	570

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Acromelic frontonasal dysostosis (AFND) [MIM:603671]: A rare variant form of frontonasal dysplasia, an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism, broadening of the nasal root, median facial cleft affecting the nose and/or upper lip and palate, unilateral or bilateral clefting of the alae nasi, lack of formation of the nasal tip, anterior cranium bifidum occultum, a V-shaped or widow's peak frontal hairline. AFND is characterized by the association of frontonasal malformations with various combinations of polydactyly, tibial hypoplasia, epibulbar dermoid, encephalocoele, corpus callosum agenesis and Dandy-Walker malformation. {ECO:0000269|PubMed:25105228}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features (NEDMAGA) [MIM:617865]: An autosomal dominant neurodevelopmental disorder characterized by infantile-onset global developmental delay, severe to profound intellectual disability, mildly delayed walking with broad-based and unsteady gait, and absence of meaningful language. Patients have features of autism, with repetitive behaviors and poor communication, but usually are socially reactive and have a happy demeanor. More variable neurologic features include mild seizures, spasticity, and peripheral neuropathy. {ECO:0000269|PubMed:29198722}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 67.03

Haploinsufficiency Scores

• pHI: 0.650
• hipred: N
• hipred_score: 0.240
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.561

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zswim6
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); growth/size/body region phenotype

Gene ontology

• Biological process: regulation of axon guidance
• Cellular component: Cul2-RING ubiquitin ligase complex
• Molecular function: zinc ion binding