MYO15A

myosin XVA, the group of FERM domain containing|Myosin heavy chains, class XV

Basic information

Region (hg38): 17:18108756-18179802

Previous symbols: [ "DFNB3", "MYO15" ]

Links

ENSG00000091536 ∙ NCBI:51168 ∙ OMIM:602666 ∙ HGNC:7594 ∙ Uniprot:Q9UKN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 3 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 3 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 3	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	17851452; 23226338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO15A gene.

• not provided (207 variants)
• Autosomal recessive nonsyndromic hearing loss 3 (81 variants)
• Rare genetic deafness (16 variants)
• Inborn genetic diseases (6 variants)
• Nonsyndromic genetic hearing loss (4 variants)
• MYO15A-related disorder (3 variants)
• Ear malformation (2 variants)
• Hearing loss, autosomal recessive (2 variants)
• Nonsyndromic genetic hearing loss;Rare genetic deafness (1 variants)
• Congenital sensorineural hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO15A 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			9	870	14	893
missense	14	38	582	75	10	719
nonsense	80	18	2			100
start loss						0
frameshift	140	35	1			176
inframe indel	2	3	10			15
splice donor/acceptor (+/-2bp)	27	54		1		82
splice region	2	1	27	110	7	147
non coding	1		29	461	90	581
Total	264	148	633	1407	114

Highest pathogenic variant AF is 0.000171

Variants in MYO15A

This is a list of pathogenic ClinVar variants found in the MYO15A region.

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

Position	Type	Phenotype	Significance	ClinVar
17-18108808-C-A		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 13, 2018)
17-18108817-G-A		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 12, 2018)
17-18108820-C-T		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 13, 2018)
17-18108821-G-T		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 13, 2018)
17-18118293-G-A			Benign (Jul 09, 2018)
17-18118568-T-C		Autosomal recessive nonsyndromic hearing loss 3	Benign (Jul 09, 2018)
17-18118598-C-T		Autosomal recessive nonsyndromic hearing loss 3	Conflicting classifications of pathogenicity (Jul 06, 2018)
17-18118628-T-A		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 13, 2018)
17-18118657-G-A		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Aug 01, 2021)
17-18118725-A-C		Autosomal recessive nonsyndromic hearing loss 3	Benign (Jun 29, 2018)
17-18118768-G-C		Autosomal recessive nonsyndromic hearing loss 3	Uncertain significance (Jan 13, 2018)
17-18118805-C-G			Likely benign (Oct 14, 2023)
17-18118809-G-A			Likely benign (Sep 27, 2022)
17-18118821-G-A			Likely benign (Dec 05, 2023)
17-18118823-A-T			Uncertain significance (Jun 24, 2021)
17-18118824-GAAGA-G			Pathogenic (May 23, 2023)
17-18118824-GAAGAAAGCC-G			Uncertain significance (Apr 19, 2023)
17-18118825-A-C		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
17-18118825-A-G			Uncertain significance (Mar 18, 2022)
17-18118827-G-A			Likely benign (Jul 31, 2023)
17-18118832-C-A			Uncertain significance (Mar 01, 2022)
17-18118833-C-G			Likely benign (Oct 09, 2023)
17-18118833-C-T			Likely benign (Sep 27, 2023)
17-18118851-G-C			Likely benign (Feb 01, 2023)
17-18118851-G-T			Likely benign (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO15A	protein_coding	protein_coding	ENST00000205890	65	71097

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.25e-56	0.910	124453	1	468	124922	0.00188

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.646	1975	2.06e+3	0.960	0.000147	22488
Missense in Polyphen		138	152.41	0.90545		1301
Synonymous	1.60	826	886	0.932	0.0000662	7280
Loss of Function	3.78	116	169	0.686	0.00000936	1848

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00371	0.00367
Ashkenazi Jewish	0.000600	0.000596
East Asian	0.00400	0.00384
Finnish	0.000559	0.000557
European (Non-Finnish)	0.00187	0.00182
Middle Eastern	0.00400	0.00384
South Asian	0.00223	0.00193
Other	0.00217	0.00214

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Required for the arrangement of stereocilia in mature hair bundles (By similarity). {ECO:0000250}.

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.0478
• rvis_EVS: -1.26
• rvis_percentile_EVS: 5.35

Haploinsufficiency Scores

• pHI: 0.381
• ghis: 0.503

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.620

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myo15
• Phenotype: vision/eye phenotype; hearing/vestibular/ear 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: sensory perception of sound;locomotory behavior;inner ear morphogenesis
• Cellular component: cytoplasm;myosin complex;stereocilium;extracellular exosome
• Molecular function: motor activity;actin binding;calmodulin binding;ATP binding