rs11570052

Variant names:

• chr11-47349863-C-G
• rs11570052
• NM_000256.3:c.565G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-47349863-C-G
• chr11-47349863-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000256.3(MYBPC3):​c.565G>C​(p.Val189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V189D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPC3 NM_000256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 35	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 35	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.565G>C	p.Val189Leu	missense_variant	Exon 5 of 34	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.565G>C		non_coding_transcript_exon_variant	Exon 5 of 27	5		ENSP00000444259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
CardioboostCm	Benign	0.044
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	0.019	D
MutationAssessor	Benign	2.0	M;.;.
PhyloP100		3.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.76	P;.;.
Vest4		0.65
MutPred		0.67		Gain of catalytic residue at V189 (P = 0.0032);Gain of catalytic residue at V189 (P = 0.0032);Gain of catalytic residue at V189 (P = 0.0032);
MVP		0.85
MPC		0.49
ClinPred		0.92	D
GERP RS		4.8
Varity_R		0.42
gMVP		0.57
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs11570052; hg19: chr11-47371414;