Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000260.4(MYO7A):c.6318G>A(p.Lys2106Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,528 control chromosomes in the GnomAD database, including 32,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5062 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27832 hom. )

Consequence

MYO7A
NM_000260.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.83

Publications

17 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-77211901-G-A is Benign according to our data. Variant chr11-77211901-G-A is described in ClinVar as Benign. ClinVar VariationId is 43324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 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	HGVSp	Effect	Exon Rank	Protein
MYO7A	NM_000260.4	MANE Select	c.6318G>A	p.Lys2106Lys	synonymous	Exon 46 of 49	NP_000251.3
MYO7A	NM_001127180.2		c.6204G>A	p.Lys2068Lys	synonymous	Exon 46 of 49	NP_001120652.1
MYO7A	NM_001369365.1		c.6171G>A	p.Lys2057Lys	synonymous	Exon 47 of 50	NP_001356294.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.6318G>A	p.Lys2106Lys	synonymous	Exon 46 of 49	ENSP00000386331.3
MYO7A	ENST00000458637.6	TSL:1	c.6204G>A	p.Lys2068Lys	synonymous	Exon 46 of 49	ENSP00000392185.2
MYO7A	ENST00000409619.6	TSL:1	c.6171G>A	p.Lys2057Lys	synonymous	Exon 47 of 50	ENSP00000386635.2

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36306

AN:

152050

Hom.:

5033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0671

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.177

AC:

44183

AN:

249168

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0695

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.188

AC:

274288

AN:

1461360

Hom.:

27832

Cov.:

AF XY:

0.185

AC XY:

134769

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.382

AC:

12799

AN:

33470

American (AMR)

AF:

0.103

AC:

4588

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3714

AN:

26134

East Asian (EAS)

AF:

0.0459

AC:

1821

AN:

39700

South Asian (SAS)

AF:

0.0893

AC:

7704

AN:

86244

European-Finnish (FIN)

AF:

0.266

AC:

14203

AN:

53390

Middle Eastern (MID)

AF:

0.235

AC:

1356

AN:

5768

European-Non Finnish (NFE)

AF:

0.195

AC:

216917

AN:

1111572

Other (OTH)

AF:

0.185

AC:

11186

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

11458

22917

34375

45834

57292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7418

14836

22254

29672

37090

<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:

0.239

AC:

36389

AN:

152168

Hom.:

5062

Cov.:

AF XY:

0.240

AC XY:

17853

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.370

AC:

15366

AN:

41506

American (AMR)

AF:

0.149

AC:

2278

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

484

AN:

3470

East Asian (EAS)

AF:

0.0672

AC:

348

AN:

5178

South Asian (SAS)

AF:

0.0852

AC:

411

AN:

4824

European-Finnish (FIN)

AF:

0.293

AC:

3107

AN:

10588

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13701

AN:

67982

Other (OTH)

AF:

0.229

AC:

483

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1367

2733

4100

5466

6833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.212

Hom.:

8144

Bravo

AF:

0.234

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.209

EpiControl

AF:

0.204

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Autosomal dominant nonsyndromic hearing loss 11 (2)

Autosomal recessive nonsyndromic hearing loss 2 (2)

not specified (2)

Usher syndrome type 1 (2)

Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.4

(source)

DANN

Benign

0.81

PhyloP100

1.8

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over