6-75835967-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004999.4(MYO6):c.553+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,583,646 control chromosomes in the GnomAD database, including 15,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1365 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14496 hom. )

Consequence

MYO6
NM_004999.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.663

Publications

9 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-75835967-T-C is Benign according to our data. Variant chr6-75835967-T-C is described in ClinVar as [Benign]. Clinvar id is 45164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO6	NM_004999.4 link	c.553+11T>C		intron_variant	Intron 7 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.553+11T>C		intron_variant	Intron 7 of 34	1	NM_004999.4	ENSP00000358994.3		Q9UM54-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19814

AN:

152130

Hom.:

1365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0373

Gnomad SAS

AF:

0.0903

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.118

AC:

29722

AN:

251136

AF XY:

0.120

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0798

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0247

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.138

AC:

197679

AN:

1431398

Hom.:

14496

Cov.:

AF XY:

0.137

AC XY:

97660

AN XY:

713956

show subpopulations

African (AFR)

AF:

0.110

AC:

3607

AN:

32866

American (AMR)

AF:

0.0833

AC:

3722

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

2739

AN:

25938

East Asian (EAS)

AF:

0.0503

AC:

1989

AN:

39526

South Asian (SAS)

AF:

0.0926

AC:

7937

AN:

85700

European-Finnish (FIN)

AF:

0.139

AC:

7403

AN:

53390

Middle Eastern (MID)

AF:

0.107

AC:

610

AN:

5704

European-Non Finnish (NFE)

AF:

0.149

AC:

161742

AN:

1084214

Other (OTH)

AF:

0.134

AC:

7930

AN:

59368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

7326

14651

21977

29302

36628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5626

11252

16878

22504

28130

<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:

0.130

AC:

19817

AN:

152248

Hom.:

1365

Cov.:

AF XY:

0.128

AC XY:

9535

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.115

AC:

4789

AN:

41548

American (AMR)

AF:

0.133

AC:

2027

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3468

East Asian (EAS)

AF:

0.0374

AC:

194

AN:

5186

South Asian (SAS)

AF:

0.0897

AC:

433

AN:

4826

European-Finnish (FIN)

AF:

0.131

AC:

1385

AN:

10594

Middle Eastern (MID)

AF:

0.137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.150

AC:

10169

AN:

68010

Other (OTH)

AF:

0.144

AC:

304

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

900

1801

2701

3602

4502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<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:

0.135

Hom.:

424

Bravo

AF:

0.128

Asia WGS

AF:

0.0680

AC:

236

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 37

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 22

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: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

Aug 10, 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

(source)

DANN

Benign

0.52

PhyloP100

-0.66

Mutation Taster

=100/0

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