10-26023496-C-T

Position:

• chr10-26023496-C-T

Variant summary

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

The NM_017433.5(MYO3A):​c.732-526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 154,008 control chromosomes in the GnomAD database, including 7,734 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 0.31 (7626 hom., cov: 32)
  • Exomes 𝑓: 0.29 (108 hom.)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3A	NM_017433.5	c.732-526C>T		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2	c.732-526C>T		intron_variant			NM_017433.5	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47245 AN: 151938 Hom.: 7624 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.288 AC: 563 AN: 1954 Hom.: 108 Cov.: 0 AF XY: 0.284 AC XY: 303 AN XY: 1068

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.311 AC: 47263 AN: 152054 Hom.: 7626 Cov.: 32 AF XY: 0.314 AC XY: 23308 AN XY: 74328

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.313

Alfa AF: 0.335 Hom.: 8538

Bravo AF: 0.290

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.73

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: rs1339816; hg19: chr10-26312425;