Variant 14-23405332-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002471.4(MYH6):c.393G>A(p.Leu131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,614,132 control chromosomes in the GnomAD database, including 5,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 400 hom., cov: 32)

Exomes 𝑓: 0.078 ( 4901 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.92

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:

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=-0.33).

BP6

Variant 14-23405332-C-T is Benign according to our data. Variant chr14-23405332-C-T is described in ClinVar as [Benign]. Clinvar id is 44495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23405332-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 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.393G>A	p.Leu131=	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.393G>A	p.Leu131=	synonymous_variant	5/39	5	NM_002471.4	ENSP00000386041	P1
MYH6	ENST00000557461.2 linkuse as main transcript	n.460G>A		non_coding_transcript_exon_variant	5/14	5

Frequencies

GnomAD3 genomes

AF:

0.0697

AC:

10614

AN:

152208

Hom.:

399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0142

Gnomad SAS

AF:

0.0781

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.0824

GnomAD3 exomes

AF:

0.0684

AC:

17198

AN:

251470

Hom.:

732

AF XY:

0.0718

AC XY:

9752

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.0420

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.0131

Gnomad SAS exome

AF:

0.0824

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0835

Gnomad OTH exome

AF:

0.0762

GnomAD4 exome

AF:

0.0783

AC:

114515

AN:

1461806

Hom.:

4901

Cov.:

AF XY:

0.0791

AC XY:

57502

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.0435

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.00957

Gnomad4 SAS exome

AF:

0.0817

Gnomad4 FIN exome

AF:

0.0490

Gnomad4 NFE exome

AF:

0.0829

Gnomad4 OTH exome

AF:

0.0803

GnomAD4 genome

AF:

0.0697

AC:

10613

AN:

152326

Hom.:

400

Cov.:

AF XY:

0.0670

AC XY:

4992

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0593

Gnomad4 AMR

AF:

0.0517

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.0781

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0847

Gnomad4 OTH

AF:

0.0820

Alfa

AF:

0.0805

Hom.:

205

Bravo

AF:

0.0694

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

EpiCase

AF:

0.0926

EpiControl

AF:

0.0899

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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 16, 2011	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	GeneDx	Oct 03, 2016	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. -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 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

-0.33

CADD

Benign

DANN

Benign

0.79

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