NM_002471.4:c.330G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002471.4(MYH6):c.330G>A(p.Ala110Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,614,156 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 33 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.42

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

MYH-6 related congenital heart defects
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 14
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
Keppen-Lubinsky syndrome
Inheritance: AD Classification: MODERATE Submitted by: Illumina
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atrial septal defect 3
Inheritance: AD Classification: LIMITED Submitted by: G2P
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 14-23405642-C-T is Benign according to our data. Variant chr14-23405642-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00464 (706/152270) while in subpopulation NFE AF = 0.00694 (472/68004). AF 95% confidence interval is 0.00642. There are 4 homozygotes in GnomAd4. There are 343 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 706 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002471.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH6	NM_002471.4	MANE Select	c.330G>A	p.Ala110Ala	synonymous	Exon 4 of 39	NP_002462.2	P13533

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH6	ENST00000405093.9	TSL:5 MANE Select	c.330G>A	p.Ala110Ala	synonymous	Exon 4 of 39	ENSP00000386041.3	P13533
MYH6	ENST00000968262.1		c.330G>A	p.Ala110Ala	synonymous	Exon 4 of 39	ENSP00000638321.1
MYH6	ENST00000968257.1		c.330G>A	p.Ala110Ala	synonymous	Exon 4 of 39	ENSP00000638316.1

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00866

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00694

Gnomad OTH

AF:

0.00479

GnomAD2 exomes

AF:

0.00388

AC:

975

AN:

251422

AF XY:

0.00386

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00771

Gnomad NFE exome

AF:

0.00609

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00574

AC:

8392

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

4016

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33480

American (AMR)

AF:

0.00150

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.000441

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00728

AC:

389

AN:

53418

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00670

AC:

7450

AN:

1112010

Other (OTH)

AF:

0.00573

AC:

346

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

512

1024

1535

2047

2559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00464

AC:

706

AN:

152270

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41560

American (AMR)

AF:

0.00399

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00866

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00694

AC:

472

AN:

68004

Other (OTH)

AF:

0.00474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00459

Hom.:

Bravo

AF:

0.00374

EpiCase

AF:

0.00545

EpiControl

AF:

0.00557

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (3)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy 14 (1)

MYH6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.12

(source)

DANN

Benign

0.83

PhyloP100

-5.4

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over