rs451794

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002471.4(MYH6):c.4011G>A(p.Ser1337Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,599,760 control chromosomes in the GnomAD database, including 9,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1337S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.077 ( 564 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9184 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -9.97

Publications

9 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=-0.62).

BP6

Variant 14-23389023-C-T is Benign according to our data. Variant chr14-23389023-C-T is described in ClinVar as Benign. ClinVar VariationId is 44501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

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.4011G>A	p.Ser1337Ser	synonymous	Exon 29 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.4011G>A	p.Ser1337Ser	synonymous	Exon 29 of 39	ENSP00000386041.3	P13533
MYH6	ENST00000968262.1		c.4044G>A	p.Ser1348Ser	synonymous	Exon 29 of 39	ENSP00000638321.1
MYH6	ENST00000968257.1		c.4011G>A	p.Ser1337Ser	synonymous	Exon 29 of 39	ENSP00000638316.1

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11538

AN:

150486

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0914

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.000400

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0856

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0763

GnomAD2 exomes

AF:

0.0770

AC:

19173

AN:

248882

AF XY:

0.0777

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.0403

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.000382

Gnomad FIN exome

AF:

0.0817

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.0913

GnomAD4 exome

AF:

0.106

AC:

153783

AN:

1449152

Hom.:

9184

Cov.:

AF XY:

0.104

AC XY:

75133

AN XY:

720476

show subpopulations

African (AFR)

AF:

0.0191

AC:

638

AN:

33392

American (AMR)

AF:

0.0425

AC:

1884

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3782

AN:

25770

East Asian (EAS)

AF:

0.000208

AC:

AN:

38544

South Asian (SAS)

AF:

0.0399

AC:

3432

AN:

86024

European-Finnish (FIN)

AF:

0.0833

AC:

4266

AN:

51188

Middle Eastern (MID)

AF:

0.0732

AC:

409

AN:

5588

European-Non Finnish (NFE)

AF:

0.121

AC:

133398

AN:

1104680

Other (OTH)

AF:

0.100

AC:

5966

AN:

59686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

8348

16695

25043

33390

41738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4716

9432

14148

18864

23580

<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:

0.0766

AC:

11544

AN:

150608

Hom.:

564

Cov.:

AF XY:

0.0752

AC XY:

5527

AN XY:

73490

show subpopulations

African (AFR)

AF:

0.0231

AC:

955

AN:

41320

American (AMR)

AF:

0.0596

AC:

902

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

505

AN:

3454

East Asian (EAS)

AF:

0.000401

AC:

AN:

4984

South Asian (SAS)

AF:

0.0338

AC:

158

AN:

4672

European-Finnish (FIN)

AF:

0.0856

AC:

871

AN:

10172

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.117

AC:

7886

AN:

67586

Other (OTH)

AF:

0.0755

AC:

158

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

510

1020

1529

2039

2549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.100

Hom.:

363

Bravo

AF:

0.0726

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.112

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (2)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.44

(source)

DANN

Benign

0.89

PhyloP100

-10

Mutation Taster

=98/2

polymorphism (auto)

(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