Genetic Variant MYO3A:c.732-526C>T (chr10-26023496-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017433.5(MYO3A):c.732-526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 154,008 control chromosomes in the GnomAD database, including 7,734 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7626 hom., cov: 32)

Exomes 𝑓: 0.29 ( 108 hom. )

Consequence

MYO3A
NM_017433.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.859

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3A	NM_017433.5 link	c.732-526C>T		intron_variant	Intron 8 of 34	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 link	c.732-526C>T		intron_variant	Intron 8 of 34		NM_017433.5	ENSP00000495965.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47245

AN:

151938

Hom.:

7624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.260

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.288

AC:

563

AN:

1954

Hom.:

108

Cov.:

AF XY:

0.284

AC XY:

303

AN XY:

1068

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.217

AC:

AN:

396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.196

AC:

AN:

South Asian (SAS)

AF:

0.365

AC:

AN:

126

European-Finnish (FIN)

AF:

0.364

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.305

AC:

392

AN:

1286

Other (OTH)

AF:

0.306

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.311

AC:

47263

AN:

152054

Hom.:

7626

Cov.:

AF XY:

0.314

AC XY:

23308

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.241

AC:

10011

AN:

41472

American (AMR)

AF:

0.260

AC:

3965

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1260

AN:

3470

East Asian (EAS)

AF:

0.257

AC:

1328

AN:

5162

South Asian (SAS)

AF:

0.430

AC:

2075

AN:

4822

European-Finnish (FIN)

AF:

0.382

AC:

4033

AN:

10570

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23591

AN:

67986

Other (OTH)

AF:

0.313

AC:

660

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1656

3311

4967

6622

8278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.333

Hom.:

10128

Bravo

AF:

0.290

Asia WGS

AF:

0.342

AC:

1189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.12

(source)

DANN

Benign

0.73

PhyloP100

-0.86

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over