rs112520797

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017433.5(MYO3A):c.409-16_409-15delAT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.06

Publications

1 publications found

Variant links:

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

MYO3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.409-16_409-15delAT		intron_variant	Intron 5 of 34	ENST00000642920.2	NP_059129.3	Q8NEV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 link	c.409-21_409-20delTA		intron_variant	Intron 5 of 34		NM_017433.5	ENSP00000495965.1		Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6517

AN:

152168

Hom.:

173

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0405

AC:

10140

AN:

250424

AF XY:

0.0416

show subpopulations

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 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

show subpopulations

African (AFR)

AF:

0.0389

AC:

1266

AN:

32504

American (AMR)

AF:

0.0263

AC:

1176

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.0577

AC:

1495

AN:

25908

East Asian (EAS)

AF:

0.00135

AC:

AN:

39326

South Asian (SAS)

AF:

0.0310

AC:

2643

AN:

85392

European-Finnish (FIN)

AF:

0.0360

AC:

1919

AN:

53304

Middle Eastern (MID)

AF:

0.0657

AC:

372

AN:

5664

European-Non Finnish (NFE)

AF:

0.0471

AC:

50769

AN:

1077782

Other (OTH)

AF:

0.0419

AC:

2477

AN:

59082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2663

5327

7990

10654

13317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1800

3600

5400

7200

9000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0428

AC:

6512

AN:

152286

Hom.:

174

Cov.:

AF XY:

0.0412

AC XY:

3069

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0396

AC:

1647

AN:

41558

American (AMR)

AF:

0.0368

AC:

562

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

200

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0277

AC:

134

AN:

4830

European-Finnish (FIN)

AF:

0.0384

AC:

407

AN:

10612

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0500

AC:

3402

AN:

68020

Other (OTH)

AF:

0.0460

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

315

630

946

1261

1576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0486

Hom.:

Bravo

AF:

0.0428

Asia WGS

AF:

0.0170

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over