rs11570058

Variant names:

Variant summary

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

The ENST00000545968.6(MYBPC3):c.786C>T(p.Thr262Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,571,980 control chromosomes in the GnomAD database, including 11,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 712 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10491 hom. )

Consequence

MYBPC3
ENST00000545968.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: -3.72

Publications

16 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=-0.83).

BP6

Variant 11-47347892-G-A is Benign according to our data. Variant chr11-47347892-G-A is described in ClinVar as Benign. ClinVar VariationId is 42793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545968.6. 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.786C>T	p.Thr262Thr	synonymous	Exon 7 of 35	NP_000247.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYBPC3	ENST00000545968.6	TSL:5 MANE Select	c.786C>T	p.Thr262Thr	synonymous	Exon 7 of 35	ENSP00000442795.1
MYBPC3	ENST00000399249.6	TSL:5	c.786C>T	p.Thr262Thr	synonymous	Exon 7 of 34	ENSP00000382193.2
MYBPC3	ENST00000544791.1	TSL:5	n.786C>T		non_coding_transcript_exon	Exon 7 of 27	ENSP00000444259.1

Frequencies

GnomAD3 genomes

AF:

0.0882

AC:

13420

AN:

152104

Hom.:

712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.0732

Gnomad ASJ

AF:

0.0951

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.0577

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.0808

GnomAD2 exomes

AF:

0.0900

AC:

16455

AN:

182798

AF XY:

0.0909

show subpopulations

Gnomad AFR exome

AF:

0.0422

Gnomad AMR exome

AF:

0.0456

Gnomad ASJ exome

AF:

0.0918

Gnomad EAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.116

AC:

165395

AN:

1419758

Hom.:

10491

Cov.:

AF XY:

0.115

AC XY:

80694

AN XY:

702194

show subpopulations

African (AFR)

AF:

0.0380

AC:

1234

AN:

32448

American (AMR)

AF:

0.0484

AC:

1856

AN:

38338

Ashkenazi Jewish (ASJ)

AF:

0.0950

AC:

2415

AN:

25422

East Asian (EAS)

AF:

0.0115

AC:

428

AN:

37264

South Asian (SAS)

AF:

0.0676

AC:

5438

AN:

80470

European-Finnish (FIN)

AF:

0.123

AC:

6195

AN:

50304

Middle Eastern (MID)

AF:

0.102

AC:

581

AN:

5674

European-Non Finnish (NFE)

AF:

0.129

AC:

141036

AN:

1090978

Other (OTH)

AF:

0.106

AC:

6212

AN:

58860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

7496

14992

22487

29983

37479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5074

10148

15222

20296

25370

<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:

0.0881

AC:

13418

AN:

152222

Hom.:

712

Cov.:

AF XY:

0.0858

AC XY:

6387

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0407

AC:

1691

AN:

41546

American (AMR)

AF:

0.0730

AC:

1117

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0951

AC:

330

AN:

3470

East Asian (EAS)

AF:

0.0178

AC:

AN:

5178

South Asian (SAS)

AF:

0.0580

AC:

280

AN:

4830

European-Finnish (FIN)

AF:

0.118

AC:

1246

AN:

10602

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8423

AN:

67978

Other (OTH)

AF:

0.0799

AC:

169

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

641

1282

1922

2563

3204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.108

Hom.:

1981

Bravo

AF:

0.0830

Asia WGS

AF:

0.0400

AC:

139

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 (4)

Hypertrophic cardiomyopathy (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Left ventricular noncompaction 10 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.23

(source)

DANN

Benign

0.60

PhyloP100

-3.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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