NM_005379.4:c.2032A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005379.4(MYO1A):c.2032A>T(p.Ile678Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,146 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 20 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:4

Conservation

PhyloP100: 1.60

Publications

14 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045950323).

BP6

Variant 12-57037571-T-A is Benign according to our data. Variant chr12-57037571-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 164588.

BS2

High AC in GnomAd4 at 397 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.2032A>T	p.Ile678Phe	missense	Exon 19 of 28	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.2032A>T	p.Ile678Phe	missense	Exon 20 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.2032A>T	p.Ile678Phe	missense	Exon 19 of 28	ENSP00000300119.3	Q9UBC5
MYO1A	ENST00000442789.6	TSL:1	c.2032A>T	p.Ile678Phe	missense	Exon 20 of 29	ENSP00000393392.2	Q9UBC5
MYO1A	ENST00000907120.1		c.2164A>T	p.Ile722Phe	missense	Exon 19 of 28	ENSP00000577179.1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

395

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00269

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00302

AC:

757

AN:

251046

AF XY:

0.00346

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00316

AC:

4613

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2378

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00116

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00417

AC:

109

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00585

AC:

505

AN:

86258

European-Finnish (FIN)

AF:

0.00730

AC:

390

AN:

53408

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00302

AC:

3354

AN:

1111990

Other (OTH)

AF:

0.00298

AC:

180

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

272

544

816

1088

1360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.00261

AC:

397

AN:

152288

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000626

AC:

AN:

41550

American (AMR)

AF:

0.00216

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0104

AC:

111

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00270

AC:

184

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.00229

Hom.:

Bravo

AF:

0.00213

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00290

AC:

352

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00302

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Congenital diarrhea (1)

Diarrhea 15, congenital (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.046

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.9

PhyloP100

1.6

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.94

Vest4

0.89

MVP

0.83

MPC

0.54

ClinPred

0.044

GERP RS

2.6

Varity_R

0.92

gMVP

0.67

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over