rs12420129

Positions:

chr11-77156089-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.468C>T(p.Ile156=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,613,478 control chromosomes in the GnomAD database, including 1,402 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 209 hom., cov: 33)

Exomes 𝑓: 0.025 ( 1193 hom. )

Consequence

MYO7A
NM_000260.4 splice_region, synonymous

Scores

Splicing: ADA: 0.9918

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 2.73

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 -15 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BP6

Variant 11-77156089-C-T is Benign according to our data. Variant chr11-77156089-C-T is described in ClinVar as [Benign]. Clinvar id is 43252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77156089-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 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.468C>T	p.Ile156=	splice_region_variant, synonymous_variant	5/49	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.468C>T	p.Ile156=	splice_region_variant, synonymous_variant	5/49	1	NM_000260.4	ENSP00000386331		Q13402-1
MYO7A	ENST00000458637.6 linkuse as main transcript	c.468C>T	p.Ile156=	splice_region_variant, synonymous_variant	5/49	1		ENSP00000392185	P1	Q13402-2
MYO7A	ENST00000409619.6 linkuse as main transcript	c.435C>T	p.Ile145=	splice_region_variant, synonymous_variant	6/50	1		ENSP00000386635		Q13402-8

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4686

AN:

152224

Hom.:

209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00545

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0964

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0455

AC:

11310

AN:

248320

Hom.:

709

AF XY:

0.0388

AC XY:

5230

AN XY:

134754

show subpopulations

Gnomad AFR exome

AF:

0.00518

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.00786

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0947

Gnomad NFE exome

AF:

0.0208

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0255

AC:

37188

AN:

1461136

Hom.:

1193

Cov.:

AF XY:

0.0242

AC XY:

17570

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00412

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.00750

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.0134

Gnomad4 FIN exome

AF:

0.0939

Gnomad4 NFE exome

AF:

0.0194

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0308

AC:

4690

AN:

152342

Hom.:

209

Cov.:

AF XY:

0.0354

AC XY:

2637

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00544

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0964

Gnomad4 NFE

AF:

0.0216

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0163

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 29, 2008	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 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. -

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	Athena Diagnostics	Aug 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Centre for Mendelian Genomics, University Medical Centre Ljubljana	Jan 16, 2020	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 recessive nonsyndromic hearing loss 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Usher syndrome type 1B

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Usher syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.030

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