rs41279908

Positions:

chr10-26096649-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.1743G>A	p.Glu581Glu	synonymous_variant	17/35	ENST00000642920.2	NP_059129.3	Q8NEV4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.1743G>A	p.Glu581Glu	synonymous_variant	17/35		NM_017433.5	ENSP00000495965.1	Q8NEV4-1
MYO3A	ENST00000543632.5 linkuse as main transcript	c.1743G>A	p.Glu581Glu	synonymous_variant	16/17	1		ENSP00000445909.1	F5H0U9
MYO3A	ENST00000642197.1 linkuse as main transcript	n.1947G>A		non_coding_transcript_exon_variant	17/27
MYO3A	ENST00000647478.1 linkuse as main transcript	n.1743G>A		non_coding_transcript_exon_variant	16/30			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

GnomAD3 exomes

AF:

0.0861

AC:

21584

AN:

250824

Hom.:

1174

AF XY:

0.0864

AC XY:

11724

AN XY:

135662

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 SAS exome

AF:

0.0372

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

Gnomad4 AFR exome

AF:

0.0775

Gnomad4 AMR exome

AF:

0.0472

Gnomad4 ASJ exome

AF:

0.0755

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.0368

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.0958

GnomAD4 genome

AF:

0.0974

AC:

14810

AN:

152032

Hom.:

799

Cov.:

AF XY:

0.0954

AC XY:

7091

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0808

Gnomad4 AMR

AF:

0.0732

Gnomad4 ASJ

AF:

0.0798

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0334

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.0888

Alfa

AF:

0.109

Hom.:

485

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

DANN

Benign

0.49

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