GeneBe

11-47335120-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000256.3(MYBPC3):​c.2827C>A​(p.Arg943Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000685 in 1,460,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYBPC3
NM_000256.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.30

Publications

0 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • left ventricular noncompaction 10
    Inheritance: AD, AR 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
  • congenital heart disease
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • dilated cardiomyopathy
    Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYBPC3
NM_000256.3
MANE Select
c.2827C>Ap.Arg943Arg
synonymous
Exon 27 of 35NP_000247.2Q14896-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYBPC3
ENST00000545968.6
TSL:5 MANE Select
c.2827C>Ap.Arg943Arg
synonymous
Exon 27 of 35ENSP00000442795.1Q14896-1
MYBPC3
ENST00000399249.6
TSL:5
c.2827C>Ap.Arg943Arg
synonymous
Exon 26 of 34ENSP00000382193.2A8MXZ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460106
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726332
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33398
American (AMR)
AF:
0.00
AC:
0
AN:
44618
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26090
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39548
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86010
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111118
Other (OTH)
AF:
0.00
AC:
0
AN:
60308
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
14
DANN
Benign
0.90
PhyloP100
6.3

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs387907267; hg19: chr11-47356671; COSMIC: COSV99920190; COSMIC: COSV99920190; API