Variant 6-75848543-ATTTTT-ATTTTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004999.4(MYO6):c.1078+19dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,609,652 control chromosomes in the GnomAD database, including 6,046 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 776 hom., cov: 31)

Exomes 𝑓: 0.074 ( 5270 hom. )

Consequence

MYO6
NM_004999.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.41

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 -16 ACMG points.

BP6

Variant 6-75848543-A-AT is Benign according to our data. Variant chr6-75848543-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 259603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 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.1078+19dupT		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.1078+19dupT		intron_variant		1	NM_004999.4	ENSP00000358994.3		Q9UM54-1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13425

AN:

151884

Hom.:

778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0743

Gnomad ASJ

AF:

0.0381

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0826

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0590

Gnomad OTH

AF:

0.0847

GnomAD3 exomes

AF:

0.0880

AC:

21733

AN:

246976

Hom.:

1490

AF XY:

0.0864

AC XY:

11568

AN XY:

133856

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.0957

Gnomad FIN exome

AF:

0.0814

Gnomad NFE exome

AF:

0.0578

Gnomad OTH exome

AF:

0.0780

GnomAD4 exome

AF:

0.0739

AC:

107776

AN:

1457652

Hom.:

5270

Cov.:

AF XY:

0.0742

AC XY:

53806

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.0702

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.0991

Gnomad4 FIN exome

AF:

0.0807

Gnomad4 NFE exome

AF:

0.0632

Gnomad4 OTH exome

AF:

0.0874

GnomAD4 genome

AF:

0.0883

AC:

13428

AN:

152000

Hom.:

776

Cov.:

AF XY:

0.0894

AC XY:

6641

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.0741

Gnomad4 ASJ

AF:

0.0381

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0826

Gnomad4 NFE

AF:

0.0590

Gnomad4 OTH

AF:

0.0852

Bravo

AF:

0.0907

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nonsyndromic Hearing Loss, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hearing loss, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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