rs55679042

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_005379.4(MYO1A):c.916G>A(p.Val306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00789 in 1,614,104 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 41 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.205

Publications

18 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.110271215).

BP6

Variant 12-57043335-C-T is Benign according to our data. Variant chr12-57043335-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 8148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 838 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4 link	c.916G>A	p.Val306Met	missense_variant	Exon 11 of 28	ENST00000300119.8	NP_005370.1	Q9UBC5
MYO1A	NM_001256041.2 link	c.916G>A	p.Val306Met	missense_variant	Exon 12 of 29		NP_001242970.1	Q9UBC5B2R643
MYO1A	XM_047428876.1 link	c.916G>A	p.Val306Met	missense_variant	Exon 12 of 29		XP_047284832.1
MYO1A	XM_011538373.3 link	c.916G>A	p.Val306Met	missense_variant	Exon 11 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO1A	ENST00000300119.8 link	c.916G>A	p.Val306Met	missense_variant	Exon 11 of 28	1	NM_005379.4	ENSP00000300119.3	Q9UBC5
MYO1A	ENST00000442789.6 link	c.916G>A	p.Val306Met	missense_variant	Exon 12 of 29	1		ENSP00000393392.2	Q9UBC5
MYO1A	ENST00000492945.5 link	c.4G>A	p.Val2Met	missense_variant	Exon 3 of 5	4		ENSP00000452229.1	G3V587
MYO1A	ENST00000554234.5 link	n.430G>A		non_coding_transcript_exon_variant	Exon 7 of 24	5		ENSP00000451033.1	G3V342

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00942

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00545

AC:

1369

AN:

251324

AF XY:

0.00544

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00931

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00814

AC:

11898

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

5731

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33480

American (AMR)

AF:

0.00331

AC:

148

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00459

AC:

120

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.00195

AC:

168

AN:

86254

European-Finnish (FIN)

AF:

0.00294

AC:

157

AN:

53418

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00975

AC:

10837

AN:

1111928

Other (OTH)

AF:

0.00639

AC:

386

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

614

1228

1842

2456

3070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.00550

AC:

838

AN:

152300

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

381

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41560

American (AMR)

AF:

0.00464

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00942

AC:

641

AN:

68018

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00797

Hom.:

Bravo

AF:

0.00554

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00965

AC:

ExAC

AF:

0.00553

AC:

672

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00818

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MYO1A: BP4, BS2 -

Jun 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27759032, 25262649, 24616153, 25333069, 12736868) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Nov 21, 2014

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 16, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Val306Met in exon 11 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 1% (83/8600) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs55679042) and due to a lack of conservation across species, including mammals. Of note, at least 6 different mammals (rat, mouse, tree shrew, pika, microbat, and wallaby) have a Methionine (Met) at this position despite high nearby amino acid conservation. -

Autosomal dominant nonsyndromic hearing loss 48

Uncertain:1

May 01, 2014

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Benign

8.2

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-1.1

N;N;.

PhyloP100

0.20

PrimateAI

Benign

0.28

PROVEAN

Benign

0.17

N;N;N

REVEL

Uncertain

0.49

Sift

Benign

0.15

T;T;T

Sift4G

Uncertain

0.045

D;D;.

Polyphen

0.0060

B;B;.

Vest4

0.14

MVP

0.60

MPC

0.088

ClinPred

0.0013

GERP RS

-1.2

Varity_R

0.066

gMVP

0.22

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over