chr11-47337820-T-C

Position:

• chr11-47337820-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000256.3(MYBPC3):​c.2309-26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). There are indicators that this mutation may affect the branch point..

• Frequency: Genomes: not found (cov: 31)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.392

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-47337820-T-C is Pathogenic according to our data. Variant chr11-47337820-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 8610.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-47337820-T-C is described in Lovd as [Likely_pathogenic]. Variant chr11-47337820-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.2309-26A>G		intron_variant		ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.2309-26A>G		intron_variant		5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.2309-26A>G		intron_variant		5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.2309-26A>G		intron_variant		5		ENSP00000444259.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypertrophic cardiomyopathy 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 1997

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	16
DANN	Benign	0.53
La Branchor		0.92
BranchPoint Hunter		7.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 5
DS_AL_spliceai		0.29		Position offset: -26

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

Publications

LitVar

Other links and lift over

dbSNP: rs886041030; hg19: chr11-47359371;