rs3831003

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004999.4(MYO6):c.1546+7_1546+8delGT variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,604,278 control chromosomes in the GnomAD database, including 746 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 72 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 674 hom. )

Consequence

MYO6
NM_004999.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.38

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 22
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, G2P
autosomal recessive nonsyndromic hearing loss 37
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 6-75861098-ATG-A is Benign according to our data. Variant chr6-75861098-ATG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO6	NM_004999.4 link	c.1546+7_1546+8delGT		splice_region_variant, intron_variant	Intron 15 of 34	ENST00000369977.8	NP_004990.3	Q9UM54-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8 link	c.1546+4_1546+5delTG		splice_region_variant, intron_variant	Intron 15 of 34	1	NM_004999.4	ENSP00000358994.3		Q9UM54-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1987

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0256

AC:

6432

AN:

251104

AF XY:

0.0244

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0329

Gnomad ASJ exome

AF:

0.00764

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.0648

Gnomad NFE exome

AF:

0.00292

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.00981

AC:

14251

AN:

1451998

Hom.:

674

AF XY:

0.00991

AC XY:

7161

AN XY:

722942

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33280

American (AMR)

AF:

0.0298

AC:

1331

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00649

AC:

169

AN:

26058

East Asian (EAS)

AF:

0.152

AC:

5984

AN:

39438

South Asian (SAS)

AF:

0.0175

AC:

1506

AN:

86018

European-Finnish (FIN)

AF:

0.0609

AC:

3237

AN:

53186

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00108

AC:

1197

AN:

1103534

Other (OTH)

AF:

0.0135

AC:

811

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

652

1304

1957

2609

3261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0131

AC:

1988

AN:

152280

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1230

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41584

American (AMR)

AF:

0.0130

AC:

199

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.146

AC:

754

AN:

5180

South Asian (SAS)

AF:

0.0205

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0695

AC:

736

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00200

AC:

136

AN:

68026

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

180

270

360

450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00702

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.0720

AC:

247

AN:

3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 14, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1546+7_1546+8del in intron 15 of MYO6: This variant is not expected to have clin ical significance because it has been identified in 16% (93/572) of Asian chromo somes by 1000 Genomes Project (dbSNP rs138200430). -

Nonsyndromic Hearing Loss, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 37;C2931767:Autosomal dominant nonsyndromic hearing loss 22

Benign:1

Jul 30, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over