NM_000260.4:c.5860C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.5860C>A(p.Leu1954Ile) variant causes a missense change. The variant allele was found at a frequency of 0.472 in 1,602,936 control chromosomes in the GnomAD database, including 184,200 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1954V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.53 ( 22476 hom., cov: 33)

Exomes 𝑓: 0.47 ( 161724 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 5.96

Publications

41 publications found

Variant links:

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
Usher syndrome type 1B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant nonsyndromic hearing loss 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.922537E-6).

BP6

Variant 11-77208433-C-A is Benign according to our data. Variant chr11-77208433-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.5860C>A	p.Leu1954Ile	missense_variant	Exon 43 of 49	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.5860C>A	p.Leu1954Ile	missense_variant	Exon 43 of 49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.5746C>A	p.Leu1916Ile	missense_variant	Exon 43 of 49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.5713C>A	p.Leu1905Ile	missense_variant	Exon 44 of 50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.3286C>A	p.Leu1096Ile	missense_variant	Exon 23 of 29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.*458C>A		non_coding_transcript_exon_variant	Exon 26 of 32			ENSP00000499323.1	A0A590UJ94
MYO7A	ENST00000670577.1 link	n.*458C>A		3_prime_UTR_variant	Exon 26 of 32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80721

AN:

151740

Hom.:

22422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.542

GnomAD2 exomes

AF:

0.474

AC:

116423

AN:

245742

AF XY:

0.461

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.468

Gnomad OTH exome

AF:

0.470

GnomAD4 exome

AF:

0.466

AC:

676045

AN:

1451080

Hom.:

161724

Cov.:

AF XY:

0.461

AC XY:

332593

AN XY:

721950

show subpopulations

African (AFR)

AF:

0.704

AC:

23416

AN:

33258

American (AMR)

AF:

0.551

AC:

24414

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

11553

AN:

26048

East Asian (EAS)

AF:

0.324

AC:

12829

AN:

39586

South Asian (SAS)

AF:

0.317

AC:

27211

AN:

85788

European-Finnish (FIN)

AF:

0.561

AC:

29854

AN:

53204

Middle Eastern (MID)

AF:

0.539

AC:

3092

AN:

5738

European-Non Finnish (NFE)

AF:

0.467

AC:

515596

AN:

1103088

Other (OTH)

AF:

0.468

AC:

28080

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

14087

28173

42260

56346

70433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15216

30432

45648

60864

76080

<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:

0.532

AC:

80841

AN:

151856

Hom.:

22476

Cov.:

AF XY:

0.532

AC XY:

39442

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.696

AC:

28870

AN:

41454

American (AMR)

AF:

0.513

AC:

7835

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1565

AN:

3470

East Asian (EAS)

AF:

0.336

AC:

1731

AN:

5148

South Asian (SAS)

AF:

0.311

AC:

1498

AN:

4818

European-Finnish (FIN)

AF:

0.569

AC:

5995

AN:

10528

Middle Eastern (MID)

AF:

0.534

AC:

155

AN:

290

European-Non Finnish (NFE)

AF:

0.468

AC:

31786

AN:

67864

Other (OTH)

AF:

0.540

AC:

1134

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.484

Hom.:

79313

Bravo

AF:

0.539

TwinsUK

AF:

0.478

AC:

1774

ALSPAC

AF:

0.461

AC:

1777

ESP6500AA

AF:

0.689

AC:

2851

ESP6500EA

AF:

0.481

AC:

4046

ExAC

AF:

0.468

AC:

56555

Asia WGS

AF:

0.362

AC:

1260

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Nov 19, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2006

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 22, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:3

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Usher syndrome type 1

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Usher syndrome type 1B

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.037

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.21

T;.;.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.45

T;T;T;T

MetaRNN

Benign

0.0000089

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.9

N;.;.;.

PhyloP100

6.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

1.9

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.15

MPC

0.091

ClinPred

0.0016

GERP RS

4.3

Varity_R

0.097

gMVP

0.13

Mutation Taster

=91/9

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over