Genetic Variant MYBPC3:c.506-12delC (chr11-47349933-AG-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000256.3(MYBPC3):c.506-12delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30296 hom., cov: 0)

Exomes 𝑓: 0.70 ( 352985 hom. )

Consequence

MYBPC3
NM_000256.3 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 0.0850

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-47349933-AG-A is Benign according to our data. Variant chr11-47349933-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 42763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-47349933-AG-A is described in Lovd as [Benign]. Variant chr11-47349933-AG-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.506-12delC		intron_variant	Intron 4 of 34	ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYBPC3	ENST00000545968.6 link	c.506-12delC	intron_variant	Intron 4 of 34	5	NM_000256.3	ENSP00000442795.1	Q14896-1
MYBPC3	ENST00000399249.6 link	c.506-12delC	intron_variant	Intron 4 of 33	5		ENSP00000382193.2	A8MXZ9
MYBPC3	ENST00000544791.1 link	n.506-12delC	intron_variant	Intron 4 of 26	5		ENSP00000444259.1	F5GZR4

Frequencies

GnomAD3 genomes

AF:

0.614

AC:

93300

AN:

151942

Hom.:

30276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.721

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.678

GnomAD3 exomes

AF:

0.665

AC:

135009

AN:

202962

Hom.:

45716

AF XY:

0.676

AC XY:

74374

AN XY:

110010

show subpopulations

Gnomad AFR exome

AF:

0.379

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.727

Gnomad EAS exome

AF:

0.628

Gnomad SAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.698

AC:

1001523

AN:

1434702

Hom.:

352985

Cov.:

AF XY:

0.700

AC XY:

497885

AN XY:

711092

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.603

Gnomad4 ASJ exome

AF:

0.725

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.709

Gnomad4 FIN exome

AF:

0.622

Gnomad4 NFE exome

AF:

0.717

Gnomad4 OTH exome

AF:

0.702

GnomAD4 genome

AF:

0.614

AC:

93369

AN:

152060

Hom.:

30296

Cov.:

AF XY:

0.612

AC XY:

45467

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.660

Gnomad4 ASJ

AF:

0.721

Gnomad4 EAS

AF:

0.647

Gnomad4 SAS

AF:

0.728

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.720

Gnomad4 OTH

AF:

0.682

Alfa

AF:

0.687

Hom.:

6634

Bravo

AF:

0.607

Asia WGS

AF:

0.709

AC:

2467

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 20, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 05, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy 4

Benign:4

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiomyopathy

Benign:2

Apr 08, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 10, 2022

Cohesion Phenomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32841044) -

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Left ventricular noncompaction 10

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Left ventricular noncompaction cardiomyopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over