chr14-23405314-C-T

Position:

chr14-23405314-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002471.4(MYH6):c.411G>A(p.Glu137Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,614,008 control chromosomes in the GnomAD database, including 48,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3915 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44921 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.342

Variant links:

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

MYH6 links:

MYH6 (HGNC:):

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 14-23405314-C-T is Benign according to our data. Variant chr14-23405314-C-T is described in ClinVar as [Benign]. Clinvar id is 44504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23405314-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.342 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.411G>A	p.Glu137Glu	synonymous_variant	5/39	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.411G>A	p.Glu137Glu	synonymous_variant	5/39	5	NM_002471.4	ENSP00000386041.3		P13533
MYH6	ENST00000557461.2 linkuse as main transcript	n.478G>A		non_coding_transcript_exon_variant	5/14	5

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33077

AN:

152074

Hom.:

3916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.207

AC:

52054

AN:

251464

Hom.:

6028

AF XY:

0.212

AC XY:

28754

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.0561

Gnomad SAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.243

AC:

354887

AN:

1461816

Hom.:

44921

Cov.:

AF XY:

0.242

AC XY:

175697

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.0475

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.236

GnomAD4 genome

AF:

0.217

AC:

33090

AN:

152192

Hom.:

3915

Cov.:

AF XY:

0.215

AC XY:

15962

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.0564

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.247

Hom.:

6247

Bravo

AF:

0.211

Asia WGS

AF:

0.122

AC:

423

AN:

3478

EpiCase

AF:

0.264

EpiControl

AF:

0.266

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 27, 2011	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 10, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.0

DANN

Benign

0.55

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