rs112520797

chr10-25997137-TTA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017433.5(MYO3A):c.409-16_409-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,575,894 control chromosomes in the GnomAD database, including 1,752 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (174 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1578 hom.)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.06

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 -16 ACMG points.

• BP6: Variant 10-25997137-TTA-T is Benign according to our data. Variant chr10-25997137-TTA-T is described in ClinVar as [Benign]. Clinvar id is 164604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3A	NM_017433.5	c.409-16_409-15del		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2	c.409-16_409-15del		intron_variant			NM_017433.5	P1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6517 AN: 152168 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0405 AC: 10140 AN: 250424 Hom.: 252 AF XY: 0.0416 AC XY: 5628 AN XY: 135358

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0570

Gnomad EAS exome AF: 0.00262

Gnomad SAS exome AF: 0.0311

Gnomad FIN exome AF: 0.0365

Gnomad NFE exome AF: 0.0533

Gnomad OTH exome AF: 0.0413

GnomAD4 exome AF: 0.0437 AC: 62170 AN: 1423608 Hom.: 1578 AF XY: 0.0438 AC XY: 31123 AN XY: 710686

Gnomad4 AFR exome AF: 0.0389

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.00135

Gnomad4 SAS exome AF: 0.0310

Gnomad4 FIN exome AF: 0.0360

Gnomad4 NFE exome AF: 0.0471

Gnomad4 OTH exome AF: 0.0419

GnomAD4 genome AF: 0.0428 AC: 6512 AN: 152286 Hom.: 174 Cov.: 32 AF XY: 0.0412 AC XY: 3069 AN XY: 74472

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0277

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0486 Hom.: 36

Bravo AF: 0.0428

Asia WGS AF: 0.0170 AC: 59 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 13, 2013	409-16_409-15delAT in intron 5 of MYO3A: This variant is not expected to have cl inical significance because it has been identified in 5.3% (445/8242) of Europea n American chromosomes and 4.1% (176/4264) of African American chromosomes from a broad population by the NHLBI Exome sequencing project, and 3.1% (69/2178) of chromosomes from the 1000 Genome Project (http://evs.gs.washington.edu/EVS/; dbS NP rs139987960). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

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: rs112520797; hg19: chr10-26286066;