NM_000260.4:c.5857-7A>T

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.5857-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,593,946 control chromosomes in the GnomAD database, including 253,876 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24040 hom., cov: 33)

Exomes 𝑓: 0.56 ( 229836 hom. )

Consequence

MYO7A
NM_000260.4 splice_region, intron

Scores

Splicing: ADA: 0.00003007

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.0280

Publications

18 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 (BayesDel_noAF=-0.93).

BP6

Variant 11-77208423-A-T is Benign according to our data. Variant chr11-77208423-A-T is described in ClinVar as Benign. ClinVar VariationId is 43303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYO7A	NM_000260.4	MANE Select	c.5857-7A>T	splice_region intron	N/A	NP_000251.3
MYO7A	NM_001127180.2		c.5743-7A>T	splice_region intron	N/A	NP_001120652.1
MYO7A	NM_001369365.1		c.5710-7A>T	splice_region intron	N/A	NP_001356294.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.5857-7A>T	splice_region intron	N/A	ENSP00000386331.3
MYO7A	ENST00000458637.6	TSL:1	c.5743-7A>T	splice_region intron	N/A	ENSP00000392185.2
MYO7A	ENST00000409619.6	TSL:1	c.5710-7A>T	splice_region intron	N/A	ENSP00000386635.2

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85030

AN:

151642

Hom.:

24002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.562

AC:

137338

AN:

244336

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.569

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.561

AC:

808682

AN:

1442188

Hom.:

229836

Cov.:

AF XY:

0.557

AC XY:

399825

AN XY:

717988

show subpopulations

African (AFR)

AF:

0.519

AC:

17147

AN:

33010

American (AMR)

AF:

0.670

AC:

29611

AN:

44196

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

13503

AN:

26002

East Asian (EAS)

AF:

0.481

AC:

19037

AN:

39542

South Asian (SAS)

AF:

0.427

AC:

36505

AN:

85488

European-Finnish (FIN)

AF:

0.651

AC:

34637

AN:

53170

Middle Eastern (MID)

AF:

0.582

AC:

3330

AN:

5722

European-Non Finnish (NFE)

AF:

0.568

AC:

622024

AN:

1095338

Other (OTH)

AF:

0.551

AC:

32888

AN:

59720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

13158

26316

39474

52632

65790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17064

34128

51192

68256

85320

<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:

0.561

AC:

85129

AN:

151758

Hom.:

24040

Cov.:

AF XY:

0.563

AC XY:

41715

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.525

AC:

21754

AN:

41400

American (AMR)

AF:

0.621

AC:

9487

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1831

AN:

3470

East Asian (EAS)

AF:

0.483

AC:

2480

AN:

5138

South Asian (SAS)

AF:

0.411

AC:

1978

AN:

4808

European-Finnish (FIN)

AF:

0.652

AC:

6859

AN:

10518

Middle Eastern (MID)

AF:

0.610

AC:

177

AN:

290

European-Non Finnish (NFE)

AF:

0.572

AC:

38799

AN:

67854

Other (OTH)

AF:

0.578

AC:

1214

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1960

3920

5880

7840

9800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.568

Hom.:

7962

Bravo

AF:

0.561

Asia WGS

AF:

0.444

AC:

1545

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

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

Mar 08, 2007

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

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

May 22, 2025

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 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

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.

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.5

(source)

DANN

Benign

0.79

PhyloP100

-0.028

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over