10-26021541-C-T

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.624C>T(p.Asp208Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 1,613,856 control chromosomes in the GnomAD database, including 6,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 514 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5899 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.73

Publications

10 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=-0.25).

BP6

Variant 10-26021541-C-T is Benign according to our data. Variant chr10-26021541-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.624C>T	p.Asp208Asp	synonymous_variant	Exon 8 of 35	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.624C>T	p.Asp208Asp	synonymous_variant	Exon 8 of 35		NM_017433.5	ENSP00000495965.1		Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0778

AC:

11837

AN:

152076

Hom.:

511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0647

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0862

Gnomad ASJ

AF:

0.0978

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0692

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.0794

GnomAD2 exomes

AF:

0.0707

AC:

17779

AN:

251384

AF XY:

0.0709

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.0557

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0952

Gnomad OTH exome

AF:

0.0808

GnomAD4 exome

AF:

0.0859

AC:

125527

AN:

1461662

Hom.:

5899

Cov.:

AF XY:

0.0845

AC XY:

61451

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.0664

AC:

2224

AN:

33480

American (AMR)

AF:

0.0588

AC:

2628

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0918

AC:

2400

AN:

26134

East Asian (EAS)

AF:

0.000403

AC:

AN:

39698

South Asian (SAS)

AF:

0.0332

AC:

2865

AN:

86256

European-Finnish (FIN)

AF:

0.0736

AC:

3929

AN:

53416

Middle Eastern (MID)

AF:

0.0505

AC:

291

AN:

5768

European-Non Finnish (NFE)

AF:

0.0956

AC:

106252

AN:

1111794

Other (OTH)

AF:

0.0815

AC:

4922

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

6332

12664

18997

25329

31661

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3758

7516

11274

15032

18790

<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:

0.0778

AC:

11845

AN:

152194

Hom.:

514

Cov.:

AF XY:

0.0762

AC XY:

5668

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0647

AC:

2688

AN:

41520

American (AMR)

AF:

0.0861

AC:

1316

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0978

AC:

339

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0288

AC:

139

AN:

4820

European-Finnish (FIN)

AF:

0.0692

AC:

733

AN:

10596

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6420

AN:

68004

Other (OTH)

AF:

0.0795

AC:

168

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

574

1147

1721

2294

2868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0868

Hom.:

395

Bravo

AF:

0.0793

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

EpiCase

AF:

0.0930

EpiControl

AF:

0.103

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp208Asp in Exon 08 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 9.6% (677/7020) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs35010955). -

Aug 03, 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. -

Autosomal recessive nonsyndromic hearing loss 30

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Jan 29, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

2.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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