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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.1743G>A	p.Glu581Glu	synonymous_variant	Exon 17 of 35	ENST00000642920.2	NP_059129.3	Q8NEV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO3A	ENST00000642920.2 link	c.1743G>A	p.Glu581Glu	synonymous_variant	Exon 17 of 35		NM_017433.5	ENSP00000495965.1	Q8NEV4-1
MYO3A	ENST00000543632.5 link	c.1743G>A	p.Glu581Glu	synonymous_variant	Exon 16 of 17	1		ENSP00000445909.1	F5H0U9
MYO3A	ENST00000642197.1 link	n.1947G>A		non_coding_transcript_exon_variant	Exon 17 of 27
MYO3A	ENST00000647478.1 link	n.1743G>A		non_coding_transcript_exon_variant	Exon 16 of 30			ENSP00000493932.1	A0A2R8Y4D5

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

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

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

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu581Glu in Exon 17 of MYO3A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 11.6% (813/7016) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs41279908). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

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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rs41279908

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