NM_000260.4:c.47T>C

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.47T>C(p.Leu16Ser) variant causes a missense change. The variant allele was found at a frequency of 0.374 in 1,609,820 control chromosomes in the GnomAD database, including 120,171 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. L16L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.47 ( 19309 hom., cov: 32)

Exomes 𝑓: 0.36 ( 100862 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: 4.72

Publications

48 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=1.2303141E-6).

BP6

Variant 11-77142737-T-C is Benign according to our data. Variant chr11-77142737-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.47T>C	p.Leu16Ser	missense_variant	Exon 3 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.47T>C	p.Leu16Ser	missense_variant	Exon 3 of 49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.47T>C	p.Leu16Ser	missense_variant	Exon 3 of 49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.14T>C	p.Leu5Ser	missense_variant	Exon 4 of 50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000660626.1 link	c.137T>C	p.Leu46Ser	missense_variant	Exon 2 of 2			ENSP00000499401.1	A0A590UJG0

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

71017

AN:

151936

Hom.:

19262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.761

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.473

GnomAD2 exomes

AF:

0.393

AC:

95355

AN:

242580

AF XY:

0.389

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.364

AC:

531187

AN:

1457764

Hom.:

100862

Cov.:

AF XY:

0.364

AC XY:

264100

AN XY:

724684

show subpopulations

African (AFR)

AF:

0.782

AC:

26157

AN:

33442

American (AMR)

AF:

0.374

AC:

16541

AN:

44196

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

9998

AN:

26076

East Asian (EAS)

AF:

0.499

AC:

19744

AN:

39560

South Asian (SAS)

AF:

0.420

AC:

35795

AN:

85200

European-Finnish (FIN)

AF:

0.288

AC:

15329

AN:

53202

Middle Eastern (MID)

AF:

0.495

AC:

2853

AN:

5768

European-Non Finnish (NFE)

AF:

0.343

AC:

380697

AN:

1110072

Other (OTH)

AF:

0.400

AC:

24073

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16057

32114

48172

64229

80286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12546

25092

37638

50184

62730

<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:

0.468

AC:

71116

AN:

152056

Hom.:

19309

Cov.:

AF XY:

0.464

AC XY:

34500

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.761

AC:

31586

AN:

41492

American (AMR)

AF:

0.376

AC:

5755

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1385

AN:

3472

East Asian (EAS)

AF:

0.504

AC:

2604

AN:

5162

South Asian (SAS)

AF:

0.428

AC:

2054

AN:

4800

European-Finnish (FIN)

AF:

0.290

AC:

3064

AN:

10578

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.340

AC:

23125

AN:

67944

Other (OTH)

AF:

0.472

AC:

999

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1727

3454

5180

6907

8634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.384

Hom.:

41196

Bravo

AF:

0.491

TwinsUK

AF:

0.343

AC:

1272

ALSPAC

AF:

0.322

AC:

1241

ESP6500AA

AF:

0.724

AC:

3006

ESP6500EA

AF:

0.342

AC:

2871

ExAC

AF:

0.399

AC:

48127

Asia WGS

AF:

0.460

AC:

1604

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:19

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Sep 18, 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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

- -

not provided

Benign:5

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1

Benign:3

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

This variant is interpreted as a Benign - Stand Alone, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

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

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

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

0.054

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.21

T;T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

0.0000012

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.2

N;.;N;.

PhyloP100

4.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

3.6

N;.;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.082

MPC

0.12

ClinPred

0.030

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.11

Mutation Taster

=99/1

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

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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