rs41279908

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_017433.5(MYO3A):c.1743G>A(p.Glu581Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,595,078 control chromosomes in the GnomAD database, including 9,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 799 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8892 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.28

Publications

5 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 10-26096649-G-A is Benign according to our data. Variant chr10-26096649-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	NM_017433.5	MANE Select	c.1743G>A	p.Glu581Glu	synonymous	Exon 17 of 35	NP_059129.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO3A	ENST00000642920.2	MANE Select	c.1743G>A	p.Glu581Glu	synonymous	Exon 17 of 35	ENSP00000495965.1
MYO3A	ENST00000543632.5	TSL:1	c.1743G>A	p.Glu581Glu	synonymous	Exon 16 of 17	ENSP00000445909.1
MYO3A	ENST00000642197.1		n.1947G>A		non_coding_transcript_exon	Exon 17 of 27

Frequencies

GnomAD3 genomes

AF:

0.0975

AC:

14818

AN:

151914

Hom.:

799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.0798

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.0898

GnomAD2 exomes

AF:

0.0861

AC:

21584

AN:

250824

AF XY:

0.0864

show subpopulations

Gnomad AFR exome

AF:

0.0782

Gnomad AMR exome

AF:

0.0452

Gnomad ASJ exome

AF:

0.0748

Gnomad EAS exome

AF:

0.00250

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.0809

GnomAD4 exome

AF:

0.105

AC:

151629

AN:

1443046

Hom.:

8892

Cov.:

AF XY:

0.103

AC XY:

74331

AN XY:

719034

show subpopulations

African (AFR)

AF:

0.0775

AC:

2565

AN:

33098

American (AMR)

AF:

0.0472

AC:

2108

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

1963

AN:

26012

East Asian (EAS)

AF:

0.00139

AC:

AN:

39538

South Asian (SAS)

AF:

0.0368

AC:

3159

AN:

85926

European-Finnish (FIN)

AF:

0.123

AC:

6572

AN:

53402

Middle Eastern (MID)

AF:

0.0673

AC:

385

AN:

5718

European-Non Finnish (NFE)

AF:

0.118

AC:

129085

AN:

1094788

Other (OTH)

AF:

0.0958

AC:

5737

AN:

59860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

6311

12621

18932

25242

31553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4508

9016

13524

18032

22540

<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:

0.0974

AC:

14810

AN:

152032

Hom.:

799

Cov.:

AF XY:

0.0954

AC XY:

7091

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0808

AC:

3354

AN:

41496

American (AMR)

AF:

0.0732

AC:

1119

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0798

AC:

277

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0334

AC:

161

AN:

4820

European-Finnish (FIN)

AF:

0.130

AC:

1363

AN:

10516

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8158

AN:

67944

Other (OTH)

AF:

0.0888

AC:

188

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

678

1357

2035

2714

3392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.108

Hom.:

486

Bravo

AF:

0.0938

Asia WGS

AF:

0.0210

AC:

AN:

3476

EpiCase

AF:

0.111

EpiControl

AF:

0.115

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Autosomal recessive nonsyndromic hearing loss 30 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.1

(source)

DANN

Benign

0.49

PhyloP100

1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over