Variant rs2295937 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_004999.4(MYO6):c.2658+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,600,182 control chromosomes in the GnomAD database, including 757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 74 hom., cov: 32)

Exomes 𝑓: 0.0099 ( 683 hom. )

Consequence

MYO6
NM_004999.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.288

Variant links:

Genes affected

MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

MYO6 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=-0.84).

BP6

Variant 6-75887014-A-C is Benign according to our data. Variant chr6-75887014-A-C is described in ClinVar as [Benign]. Clinvar id is 45148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO6	NM_004999.4 linkuse as main transcript	c.2658+20A>C		intron_variant		ENST00000369977.8	NP_004990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8 linkuse as main transcript	c.2658+20A>C		intron_variant		1	NM_004999.4	ENSP00000358994	A1	Q9UM54-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1995

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0699

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0257

AC:

6435

AN:

250096

Hom.:

316

AF XY:

0.0245

AC XY:

3320

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.000313

Gnomad AMR exome

AF:

0.0330

Gnomad ASJ exome

AF:

0.00765

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.0191

Gnomad FIN exome

AF:

0.0650

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.00994

AC:

14386

AN:

1447900

Hom.:

683

Cov.:

AF XY:

0.0100

AC XY:

7220

AN XY:

721258

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.00661

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0612

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0131

AC:

1996

AN:

152282

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1234

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0129

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0699

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00467

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.0720

AC:

250

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 23, 2010

Changed to benign based on frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

DANN

Benign

0.38

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