Genetic Variant MYO1A:p.Glu126Lys (chr12-57047357-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005379.4(MYO1A):c.376G>A(p.Glu126Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,614,194 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.48

Publications

6 publications found

Variant links:

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

MYO1A Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYO1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055823).

BP6

Variant 12-57047357-C-T is Benign according to our data. Variant chr12-57047357-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 178456.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 82 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	NM_005379.4	MANE Select	c.376G>A	p.Glu126Lys	missense	Exon 5 of 28	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.376G>A	p.Glu126Lys	missense	Exon 6 of 29	NP_001242970.1	Q9UBC5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYO1A	ENST00000300119.8	TSL:1 MANE Select	c.376G>A	p.Glu126Lys	missense	Exon 5 of 28	ENSP00000300119.3	Q9UBC5
MYO1A	ENST00000442789.6	TSL:1	c.376G>A	p.Glu126Lys	missense	Exon 6 of 29	ENSP00000393392.2	Q9UBC5
MYO1A	ENST00000907120.1		c.508G>A	p.Glu170Lys	missense	Exon 5 of 28	ENSP00000577179.1

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000482

AC:

121

AN:

250812

AF XY:

0.000421

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000945

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00125

AC:

1827

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

841

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00154

AC:

1710

AN:

1112008

Other (OTH)

AF:

0.00171

AC:

103

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

100

199

299

398

498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.000538

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41558

American (AMR)

AF:

0.0000653

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000968

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.00147

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.040

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.32

MutationAssessor

Benign

0.24

PhyloP100

4.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.36

Sift

Benign

0.75

Sift4G

Benign

0.66

Polyphen

0.98

Vest4

0.38

MVP

0.85

MPC

0.11

ClinPred

0.041

GERP RS

5.2

Varity_R

0.12

gMVP

0.45

Mutation Taster

=291/9

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over