rs12764197

Variant names:

• chr10-26195225-A-G
• rs12764197
• NM_017433.5:c.4545+1914A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-26195225-A-G
• chr10-26195225-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017433.5(MYO3A):​c.4545+1914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,004 control chromosomes in the GnomAD database, including 3,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3747 hom., cov: 32)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 6 publications found

Genes affected

MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

MYO3A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 30

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal dominant 90

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	NM_017433.5	MANE Select	c.4545+1914A>G		intron	N/A	NP_059129.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	ENST00000642920.2	MANE Select	c.4545+1914A>G		intron	N/A	ENSP00000495965.1
	MYO3A	ENST00000543632.5	TSL:1	c.1777-16618A>G		intron	N/A	ENSP00000445909.1
	MYO3A	ENST00000647478.1		n.*1500+1914A>G		intron	N/A	ENSP00000493932.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31260 AN: 151886 Hom.: 3734 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31310 AN: 152004 Hom.: 3747 Cov.: 32 AF XY: 0.207 AC XY: 15401 AN XY: 74312

African (AFR) AF: 0.319 AC: 13200 AN: 41394

American (AMR) AF: 0.206 AC: 3152 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1575 AN: 5150

South Asian (SAS) AF: 0.171 AC: 824 AN: 4816

European-Finnish (FIN) AF: 0.194 AC: 2053 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9477 AN: 67980

Other (OTH) AF: 0.200 AC: 422 AN: 2110

Alfa AF: 0.173 Hom.: 5413

Bravo AF: 0.215

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.79
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12764197; hg19: chr10-26484154;