Variant chr10-26021668-G-A 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_001368265.1(MYO3A):c.*7G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,613,526 control chromosomes in the GnomAD database, including 6,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 417 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5769 hom. )

Consequence

MYO3A
NM_001368265.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.336

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 10-26021668-G-A is Benign according to our data. Variant chr10-26021668-G-A is described in ClinVar as [Benign]. Clinvar id is 260812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-26021668-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 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.731+20G>A		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.731+20G>A		intron_variant			NM_017433.5	ENSP00000495965.1		Q8NEV4-1

Frequencies

GnomAD3 genomes

AF:

0.0664

AC:

10094

AN:

152102

Hom.:

416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0756

Gnomad ASJ

AF:

0.0977

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0940

Gnomad OTH

AF:

0.0738

GnomAD3 exomes

AF:

0.0674

AC:

16943

AN:

251272

Hom.:

758

AF XY:

0.0683

AC XY:

9282

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.0520

Gnomad ASJ exome

AF:

0.0926

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0320

Gnomad FIN exome

AF:

0.0699

Gnomad NFE exome

AF:

0.0949

Gnomad OTH exome

AF:

0.0797

GnomAD4 exome

AF:

0.0844

AC:

123400

AN:

1461306

Hom.:

5769

Cov.:

AF XY:

0.0832

AC XY:

60508

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.0547

Gnomad4 ASJ exome

AF:

0.0918

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0330

Gnomad4 FIN exome

AF:

0.0734

Gnomad4 NFE exome

AF:

0.0953

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0663

AC:

10095

AN:

152220

Hom.:

417

Cov.:

AF XY:

0.0645

AC XY:

4802

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.0977

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0286

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0939

Gnomad4 OTH

AF:

0.0739

Alfa

AF:

0.0817

Hom.:

253

Bravo

AF:

0.0665

Asia WGS

AF:

0.0310

AC:

110

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: -20

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