rs77625410

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.5156A>G(p.Tyr1719Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,552,260 control chromosomes in the GnomAD database, including 770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 369 hom., cov: 32)

Exomes 𝑓: 0.012 ( 401 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 8.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002670139).

BP6

Variant 11-77202412-A-G is Benign according to our data. Variant chr11-77202412-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 43274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77202412-A-G is described in Lovd as [Benign]. Variant chr11-77202412-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.5156A>G	p.Tyr1719Cys	missense_variant	Exon 37 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.5156A>G	p.Tyr1719Cys	missense_variant	Exon 37 of 49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.5042A>G	p.Tyr1681Cys	missense_variant	Exon 37 of 49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.5009A>G	p.Tyr1670Cys	missense_variant	Exon 38 of 50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.2582A>G	p.Tyr861Cys	missense_variant	Exon 17 of 29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.2996A>G		non_coding_transcript_exon_variant	Exon 20 of 32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6829

AN:

152074

Hom.:

360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00851

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0403

GnomAD3 exomes

AF:

0.0161

AC:

2528

AN:

157078

Hom.:

AF XY:

0.0139

AC XY:

1160

AN XY:

83184

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00662

Gnomad FIN exome

AF:

0.00523

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0121

AC:

16918

AN:

1400068

Hom.:

401

Cov.:

AF XY:

0.0117

AC XY:

8103

AN XY:

690672

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0184

Gnomad4 ASJ exome

AF:

0.0123

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.00716

Gnomad4 FIN exome

AF:

0.00535

Gnomad4 NFE exome

AF:

0.00894

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0451

AC:

6871

AN:

152192

Hom.:

369

Cov.:

AF XY:

0.0431

AC XY:

3206

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.0260

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00852

Gnomad4 FIN

AF:

0.00650

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0399

Alfa

AF:

0.0153

Hom.:

114

Bravo

AF:

0.0499

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.111

AC:

448

ESP6500EA

AF:

0.00896

AC:

ExAC

AF:

0.0109

AC:

1117

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 06, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 28, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

Feb 06, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 23, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 05, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Usher syndrome type 1

Benign:2

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, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. 6 homozygotes in ExAC. -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Usher syndrome type 1B

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:1

Apr 28, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Jan 01, 2009

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;.;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D;D

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Pathogenic

3.0

M;.;.;.

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Uncertain

0.49

Sift

Benign

0.056

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.90

P;.;.;.

Vest4

0.83

MPC

0.48

ClinPred

0.016

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.46

gMVP

0.60

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

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