10-25997230-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017433.5(MYO3A):c.480G>T(p.Thr160Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,612,676 control chromosomes in the GnomAD database, including 3,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T160T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.095 ( 1226 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2535 hom. )

Consequence

MYO3A
NM_017433.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.91

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-25997230-G-T is Benign according to our data. Variant chr10-25997230-G-T is described in ClinVar as Benign. ClinVar VariationId is 45817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.480G>T	p.Thr160Thr	synonymous_variant	Exon 6 of 35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 link	c.480G>T	p.Thr160Thr	synonymous_variant	Exon 6 of 35		NM_017433.5	ENSP00000495965.1

Frequencies

GnomAD3 genomes

AF:

0.0951

AC:

14455

AN:

152034

Hom.:

1219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0664

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0835

GnomAD2 exomes

AF:

0.0542

AC:

13596

AN:

250992

AF XY:

0.0517

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0364

Gnomad ASJ exome

AF:

0.0575

Gnomad EAS exome

AF:

0.00261

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0541

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0494

AC:

72135

AN:

1460526

Hom.:

2535

Cov.:

AF XY:

0.0487

AC XY:

35363

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.220

AC:

7359

AN:

33400

American (AMR)

AF:

0.0394

AC:

1763

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1536

AN:

26108

East Asian (EAS)

AF:

0.00134

AC:

AN:

39562

South Asian (SAS)

AF:

0.0312

AC:

2692

AN:

86232

European-Finnish (FIN)

AF:

0.0360

AC:

1921

AN:

53400

Middle Eastern (MID)

AF:

0.0763

AC:

439

AN:

5756

European-Non Finnish (NFE)

AF:

0.0478

AC:

53136

AN:

1111010

Other (OTH)

AF:

0.0536

AC:

3236

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

3249

6498

9747

12996

16245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2004

4008

6012

8016

10020

<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:

0.0952

AC:

14486

AN:

152150

Hom.:

1226

Cov.:

AF XY:

0.0932

AC XY:

6931

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.217

AC:

9014

AN:

41474

American (AMR)

AF:

0.0663

AC:

1014

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

200

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4816

European-Finnish (FIN)

AF:

0.0387

AC:

410

AN:

10598

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0510

AC:

3469

AN:

68002

Other (OTH)

AF:

0.0826

AC:

174

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

627

1254

1880

2507

3134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0642

Hom.:

749

Bravo

AF:

0.102

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: 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.

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

Thr160Thr in Exon 06 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 21.5% (802/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs12257119).

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.090

(source)

DANN

Benign

0.35

PhyloP100

-1.9

Mutation Taster

=100/0

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