rs2276288

Positions:

chr11-77201591-A-T

Variant summary

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

The NM_000260.4(MYO7A):c.4996A>T(p.Ser1666Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,613,536 control chromosomes in the GnomAD database, including 246,230 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1666G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.59 ( 26742 hom., cov: 31)

Exomes 𝑓: 0.54 ( 219488 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.52

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=6.6471216E-6).

BP6

Variant 11-77201591-A-T is Benign according to our data. Variant chr11-77201591-A-T is described in ClinVar as [Benign]. Clinvar id is 43269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77201591-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.4996A>T	p.Ser1666Cys	missense_variant	36/49	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.4996A>T	p.Ser1666Cys	missense_variant	36/49	1	NM_000260.4	ENSP00000386331		Q13402-1

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89174

AN:

151850

Hom.:

26687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.584

GnomAD3 exomes

AF:

0.550

AC:

136951

AN:

249010

Hom.:

38891

AF XY:

0.535

AC XY:

72299

AN XY:

135100

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.671

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.627

Gnomad NFE exome

AF:

0.550

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.544

AC:

795340

AN:

1461568

Hom.:

219488

Cov.:

AF XY:

0.538

AC XY:

390875

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.685

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.434

Gnomad4 EAS exome

AF:

0.472

Gnomad4 SAS exome

AF:

0.372

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.588

AC:

89296

AN:

151968

Hom.:

26742

Cov.:

AF XY:

0.588

AC XY:

43660

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.687

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.441

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.544

Hom.:

17241

Bravo

AF:

0.596

TwinsUK

AF:

0.562

AC:

2085

ALSPAC

AF:

0.552

AC:

2126

ESP6500AA

AF:

0.681

AC:

2919

ESP6500EA

AF:

0.543

AC:

4591

ExAC

AF:

0.543

AC:

65799

Asia WGS

AF:

0.435

AC:

1515

AN:

3478

EpiCase

AF:

0.541

EpiControl

AF:

0.539

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 08, 2007	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 22, 2014	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 25342930, 19320733, 21569298) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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 dominant nonsyndromic hearing loss 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

Usher syndrome type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

Usher syndrome type 1B

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.078

DEOGEN2

Benign

0.21

T;.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.13

T;T;T;T

MetaRNN

Benign

0.0000066

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

N;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

5.5

N;N;N;N

REVEL

Benign

0.048

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.86

T;T;T;T

Vest4

0.23

MPC

0.082

ClinPred

0.0031

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.32

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