Genetic Variant NM_004999.4:c.-47-179delA (chr6-75817304-CA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004999.4(MYO6):c.-47-179delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene MYO6 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0044 ( 0 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

MYO6
NM_004999.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, ClinGen
autosomal recessive nonsyndromic hearing loss 37
Inheritance: AR Classification: STRONG, MODERATE Submitted by: 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

Specifications for MYO6 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO6	NM_004999.4	MANE Select	c.-47-179delA	intron	N/A	NP_004990.3
MYO6	NM_001368865.1		c.-47-179delA	intron	N/A	NP_001355794.1	A0A590UJ40
MYO6	NM_001368866.1		c.-47-179delA	intron	N/A	NP_001355795.1	A0A1Y0BRN3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYO6	ENST00000369977.8	TSL:1 MANE Select	c.-47-196delA	intron	N/A	ENSP00000358994.3	Q9UM54-1
MYO6	ENST00000664640.1		c.-47-196delA	intron	N/A	ENSP00000499278.1	A0A590UJ40
MYO6	ENST00000947981.1		c.-47-196delA	intron	N/A	ENSP00000618040.1

Frequencies

GnomAD3 genomes

AF:

0.00445

AC:

280

AN:

62954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00567

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00435

Gnomad SAS

AF:

0.0487

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.00296

Gnomad OTH

AF:

0.00827

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00443

AC:

279

AN:

62974

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

173

AN XY:

29676

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

19264

American (AMR)

AF:

0.00567

AC:

AN:

5292

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

1514

East Asian (EAS)

AF:

0.00437

AC:

AN:

2748

South Asian (SAS)

AF:

0.0484

AC:

103

AN:

2130

European-Finnish (FIN)

AF:

0.00650

AC:

AN:

2770

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00296

AC:

AN:

28048

Other (OTH)

AF:

0.00818

AC:

AN:

856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over