rs12764197

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.4545+1914A>G		intron_variant		ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2	c.4545+1914A>G		intron_variant			NM_017433.5	ENSP00000495965	P1
MYO3A	ENST00000543632.5	c.1777-16618A>G		intron_variant		1		ENSP00000445909
MYO3A	ENST00000647478.1	c.*1500+1914A>G		intron_variant, NMD_transcript_variant				ENSP00000493932

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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.200

Alfa AF: 0.191 Hom.: 906

Bravo AF: 0.215

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs12764197; hg19: chr10-26484154;