Variant chr10-25997137-TTA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017433.5(MYO3A):c.409-16_409-15delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,575,894 control chromosomes in the GnomAD database, including 1,752 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 174 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1578 hom. )

Consequence

MYO3A
NM_017433.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.06

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 links:

MYO3A (HGNC:):

MYO3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-25997137-TTA-T is Benign according to our data. Variant chr10-25997137-TTA-T is described in ClinVar as [Benign]. Clinvar id is 164604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.409-16_409-15delAT		intron_variant		ENST00000642920.2	NP_059129.3	Q8NEV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.409-16_409-15delAT		intron_variant			NM_017433.5	ENSP00000495965.1		Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6517

AN:

152168

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0368

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0277

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0465

GnomAD3 exomes

AF:

0.0405

AC:

10140

AN:

250424

Hom.:

252

AF XY:

0.0416

AC XY:

5628

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.0255

Gnomad ASJ exome

AF:

0.0570

Gnomad EAS exome

AF:

0.00262

Gnomad SAS exome

AF:

0.0311

Gnomad FIN exome

AF:

0.0365

Gnomad NFE exome

AF:

0.0533

Gnomad OTH exome

AF:

0.0413

GnomAD4 exome

AF:

0.0437

AC:

62170

AN:

1423608

Hom.:

1578

AF XY:

0.0438

AC XY:

31123

AN XY:

710686

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.0263

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.00135

Gnomad4 SAS exome

AF:

0.0310

Gnomad4 FIN exome

AF:

0.0360

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0419

GnomAD4 genome

AF:

0.0428

AC:

6512

AN:

152286

Hom.:

174

Cov.:

AF XY:

0.0412

AC XY:

3069

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0396

Gnomad4 AMR

AF:

0.0368

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0277

Gnomad4 FIN

AF:

0.0384

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0486

Hom.:

Bravo

AF:

0.0428

Asia WGS

AF:

0.0170

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 13, 2013	409-16_409-15delAT in intron 5 of MYO3A: This variant is not expected to have cl inical significance because it has been identified in 5.3% (445/8242) of Europea n American chromosomes and 4.1% (176/4264) of African American chromosomes from a broad population by the NHLBI Exome sequencing project, and 3.1% (69/2178) of chromosomes from the 1000 Genome Project (http://evs.gs.washington.edu/EVS/; dbS NP rs139987960). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over