rs11014993

Positions:

• chr10-26194254-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017433.5(MYO3A):​c.4545+943T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,040 control chromosomes in the GnomAD database, including 4,288 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 0.24 (4288 hom., cov: 32)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5	c.4545+943T>C		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+943T>C		intron_variant			NM_017433.5	ENSP00000495965	P1
MYO3A	ENST00000543632.5	c.1777-17589T>C		intron_variant		1		ENSP00000445909
MYO3A	ENST00000647478.1	c.*1500+943T>C		intron_variant, NMD_transcript_variant				ENSP00000493932

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35761 AN: 151922 Hom.: 4283 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.235 AC: 35785 AN: 152040 Hom.: 4288 Cov.: 32 AF XY: 0.238 AC XY: 17712 AN XY: 74294

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.235

Alfa AF: 0.224 Hom.: 5226

Bravo AF: 0.236

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.60

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: rs11014993; hg19: chr10-26483183;