rs111033223

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.3503+12_3503+33del (p.Gly1172GlufsX34) variant in the MYO7A gene is 50.8% (11084/21494) of European (Finnish) chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA132294/MONDO:0019497/005

Frequency

Genomes: 𝑓 0.45 ( 16051 hom., cov: 0)

Exomes 𝑓: 0.46 ( 154611 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Not classified

Clinical Significance

Benign reviewed by expert panel B:10

Conservation

PhyloP100: 1.09

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 links:

MYO7A (HGNC:):

MYO7A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.3503+12_3503+33delGAGGCGGGGACACCAGGGCCTG		intron_variant		ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.3503+12_3503+33delGAGGCGGGGACACCAGGGCCTG	intron_variant	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 linkuse as main transcript	c.3503+12_3503+33delGAGGCGGGGACACCAGGGCCTG	intron_variant	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 linkuse as main transcript	c.3470+12_3470+33delGAGGCGGGGACACCAGGGCCTG	intron_variant	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 linkuse as main transcript	c.1046+12_1046+33delGAGGCGGGGACACCAGGGCCTG	intron_variant	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 linkuse as main transcript	n.1343+12_1343+33delGAGGCGGGGACACCAGGGCCTG	intron_variant			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69092

AN:

151924

Hom.:

16041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.434

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.380

AC:

76594

AN:

201658

Hom.:

16257

AF XY:

0.368

AC XY:

40024

AN XY:

108766

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.427

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.456

AC:

649803

AN:

1426072

Hom.:

154611

AF XY:

0.449

AC XY:

317982

AN XY:

707850

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.339

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.571

Gnomad4 NFE exome

AF:

0.476

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.455

AC:

69133

AN:

152042

Hom.:

16051

Cov.:

AF XY:

0.456

AC XY:

33879

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.434

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.594

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.449

Hom.:

2801

Bravo

AF:

0.447

Asia WGS

AF:

0.329

AC:

1144

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 14, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 05, 2012	See NM_000260 c.3503+12_3503+33del -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 19, 2015	- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Usher syndrome type 1B

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 25, 2019

- -

Nonsyndromic genetic hearing loss

Benign:1

Benign, reviewed by expert panel

curation

ClinGen Hearing Loss Variant Curation Expert Panel

Sep 28, 2018

The filtering allele frequency of the c.3503+12_3503+33del (p.Gly1172GlufsX34) variant in the MYO7A gene is 50.8% (11084/21494) of European (Finnish) chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Usher syndrome type 1;C1832475:Autosomal dominant nonsyndromic hearing loss 11;C1838701:Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over