rs886037901

Variant names:

• chr11-47350572-C-CTCAG
• rs886037901
• NM_000256.3:c.332_335dupCTGA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000256.3(MYBPC3):​c.332_335dupCTGA​(p.Glu112AspfsTer2) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPC3 NM_000256.3 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.0570

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-47350572-C-CTCAG is Pathogenic according to our data. Variant chr11-47350572-C-CTCAG is described in ClinVar as [Pathogenic]. Clinvar id is 254154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.332_335dupCTGA	p.Glu112AspfsTer2	frameshift_variant, stop_gained	Exon 3 of 35	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.332_335dupCTGA	p.Glu112AspfsTer2	frameshift_variant, stop_gained	Exon 3 of 35	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.332_335dupCTGA	p.Glu112AspfsTer2	frameshift_variant, stop_gained	Exon 3 of 34	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.332_335dupCTGA		non_coding_transcript_exon_variant	Exon 3 of 27	5		ENSP00000444259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic cardiomyopathy 4 Pathogenic:1

Jan 01, 2016

Center for Medical Genetics Ghent, University of Ghent

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server) and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886037901; hg19: chr11-47372123;