Variant rs12210963 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.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

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:

MYO6 (HGNC:):

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=-0.79).

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. Variant chr6-75835967-T-C is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
MYO6	NM_004999.4 linkuse as main transcript	c.553+11T>C		intron_variant		ENST00000369977.8	NP_004990.3	Q9UM54-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8 linkuse as main transcript	c.553+11T>C		intron_variant		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

GnomAD3 exomes

AF:

0.118

AC:

29722

AN:

251136

Hom.:

1979

AF XY:

0.120

AC XY:

16299

AN XY:

135740

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 SAS exome

AF:

0.0950

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

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0833

Gnomad4 ASJ exome

AF:

0.106

Gnomad4 EAS exome

AF:

0.0503

Gnomad4 SAS exome

AF:

0.0926

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.130

AC:

19817

AN:

152248

Hom.:

1365

Cov.:

AF XY:

0.128

AC XY:

9535

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.0374

Gnomad4 SAS

AF:

0.0897

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.135

Hom.:

414

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 19, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

Autosomal recessive nonsyndromic hearing loss 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.3

DANN

Benign

0.52

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