Variant rs17739680 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017433.5(MYO3A):c.4438+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,611,870 control chromosomes in the GnomAD database, including 9,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 784 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8961 hom. )

Consequence

MYO3A
NM_017433.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.204

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-26176863-T-C is Benign according to our data. Variant chr10-26176863-T-C is described in ClinVar as [Benign]. Clinvar id is 260811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.4438+18T>C		intron_variant		ENST00000642920.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.4438+18T>C	intron_variant		NM_017433.5	P1	Q8NEV4-1
MYO3A	ENST00000543632.5 linkuse as main transcript	c.1777-34980T>C	intron_variant	1
MYO3A	ENST00000647478.1 linkuse as main transcript	c.*1393+6324T>C	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0966

AC:

14691

AN:

152110

Hom.:

784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0812

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.0712

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.0889

GnomAD3 exomes

AF:

0.0850

AC:

21336

AN:

250886

Hom.:

1149

AF XY:

0.0854

AC XY:

11584

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0785

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.0731

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.0800

GnomAD4 exome

AF:

0.105

AC:

153890

AN:

1459642

Hom.:

8961

Cov.:

AF XY:

0.104

AC XY:

75281

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.0790

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.0745

Gnomad4 EAS exome

AF:

0.00136

Gnomad4 SAS exome

AF:

0.0369

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.0954

GnomAD4 genome

AF:

0.0965

AC:

14683

AN:

152228

Hom.:

784

Cov.:

AF XY:

0.0945

AC XY:

7036

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0809

Gnomad4 AMR

AF:

0.0711

Gnomad4 ASJ

AF:

0.0776

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0337

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.0880

Alfa

AF:

0.102

Hom.:

162

Bravo

AF:

0.0929

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.5

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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