rs1052373

Variant names:

Variant summary

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

The NM_000256.3(MYBPC3):c.3288G>A(p.Glu1096Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,589,804 control chromosomes in the GnomAD database, including 104,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12430 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91846 hom. )

Consequence

MYBPC3
NM_000256.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: 0.00300

Publications

59 publications found

Variant links:

Genes affected

MYBPC3 (HGNC:7551): (myosin binding protein C3) MYBPC3 encodes the cardiac isoform of myosin-binding protein C. Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. MYBPC3 is expressed exclusively in heart muscle and is a key regulator of cardiac contraction. Mutations in this gene are a frequent cause of familial hypertrophic cardiomyopathy. [provided by RefSeq, May 2022]

MYBPC3 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 4
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
left ventricular noncompaction 10
Inheritance: AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
atrial fibrillation
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYBPC3 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 11-47333236-C-T is Benign according to our data. Variant chr11-47333236-C-T is described in ClinVar as Benign. ClinVar VariationId is 42700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.003 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	NM_000256.3	MANE Select	c.3288G>A	p.Glu1096Glu	synonymous	Exon 30 of 35	NP_000247.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC3	ENST00000545968.6	TSL:5 MANE Select	c.3288G>A	p.Glu1096Glu	synonymous	Exon 30 of 35	ENSP00000442795.1
	MYBPC3	ENST00000399249.6	TSL:5	c.3288G>A	p.Glu1096Glu	synonymous	Exon 29 of 34	ENSP00000382193.2

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59338

AN:

151892

Hom.:

12433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.401

AC:

84300

AN:

210138

AF XY:

0.396

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.441

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.699

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.318

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.348

AC:

500034

AN:

1437794

Hom.:

91846

Cov.:

AF XY:

0.349

AC XY:

248932

AN XY:

712858

show subpopulations

African (AFR)

AF:

0.494

AC:

16321

AN:

33048

American (AMR)

AF:

0.425

AC:

17525

AN:

41230

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6779

AN:

25664

East Asian (EAS)

AF:

0.688

AC:

26626

AN:

38700

South Asian (SAS)

AF:

0.463

AC:

38219

AN:

82604

European-Finnish (FIN)

AF:

0.413

AC:

21311

AN:

51648

Middle Eastern (MID)

AF:

0.265

AC:

1521

AN:

5732

European-Non Finnish (NFE)

AF:

0.319

AC:

350783

AN:

1099714

Other (OTH)

AF:

0.352

AC:

20949

AN:

59454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18655

37310

55966

74621

93276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11868

23736

35604

47472

59340

<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:

0.390

AC:

59358

AN:

152010

Hom.:

12430

Cov.:

AF XY:

0.399

AC XY:

29637

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.492

AC:

20373

AN:

41444

American (AMR)

AF:

0.355

AC:

5420

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

928

AN:

3468

East Asian (EAS)

AF:

0.686

AC:

3539

AN:

5160

South Asian (SAS)

AF:

0.467

AC:

2244

AN:

4810

European-Finnish (FIN)

AF:

0.429

AC:

4538

AN:

10584

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21377

AN:

67942

Other (OTH)

AF:

0.334

AC:

705

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1800

3599

5399

7198

8998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.333

Hom.:

31082

Bravo

AF:

0.387

Asia WGS

AF:

0.530

AC:

1841

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Hypertrophic cardiomyopathy 4 (5)

Cardiomyopathy (2)

Left ventricular noncompaction 10 (2)

not provided (2)

Cardiovascular phenotype (1)

Hypertrophic cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.5

(source)

DANN

Benign

0.69

PhyloP100

0.0030

Mutation Taster

=100/0

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

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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over