Variant rs1402918571 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6_Moderate

The NM_004999.4(MYO6):c.887A>G(p.Lys296Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,459,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

MYO6
NM_004999.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34789002).

BP6

Variant 6-75844967-A-G is Benign according to our data. Variant chr6-75844967-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 517276.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO6	NM_004999.4 linkuse as main transcript	c.887A>G	p.Lys296Arg	missense_variant	10/35	ENST00000369977.8	NP_004990.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO6	ENST00000369977.8 linkuse as main transcript	c.887A>G	p.Lys296Arg	missense_variant	10/35	1	NM_004999.4	ENSP00000358994	A1	Q9UM54-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251102

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1459596

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 16, 2017

p.Lys296Arg in exon 10 of MYO6: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, 3 mammals (squirrel, lesser Egyptian jerboa, and horse) have an arginine (A rg) at this position despite high nearby amino acid conservation. Furthermore, c omputational prediction tools do not suggest a likely impact to the protein. It has been identified in 2/17248 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomAD.broadinstitute.org). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;.;.;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;.;T;D;D;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.35

T;T;T;T;T;T

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

1.5

.;L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

N;N;N;.;N;.

REVEL

Uncertain

0.55

Sift

Benign

0.19

T;T;T;.;T;.

Sift4G

Benign

0.52

T;T;T;T;T;T

Polyphen

0.96, 0.97

.;D;D;D;.;.

Vest4

0.29

MutPred

0.33

Loss of ubiquitination at K296 (P = 0.0134);Loss of ubiquitination at K296 (P = 0.0134);Loss of ubiquitination at K296 (P = 0.0134);Loss of ubiquitination at K296 (P = 0.0134);Loss of ubiquitination at K296 (P = 0.0134);Loss of ubiquitination at K296 (P = 0.0134);

MVP

0.86

MPC

0.21

ClinPred

0.26

GERP RS

4.1

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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