11-47338618-G-T

Position:

• chr11-47338618-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_000256.3(MYBPC3):​c.2210C>A​(p.Thr737Lys) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPC3 NM_000256.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

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 4 ACMG points.

• PM1: In a strand (size 4) in uniprot entity MYPC3_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000256.3
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.2210C>A	p.Thr737Lys	missense_variant	23/35	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.2210C>A	p.Thr737Lys	missense_variant	23/35	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.2210C>A	p.Thr737Lys	missense_variant	22/34	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.2210C>A		non_coding_transcript_exon_variant	23/27	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	Uncertain	0.44
CardioboostCm	Benign	0.010
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Uncertain	0.36
Sift	Benign	0.10	T;.;T
Sift4G	Uncertain	0.018	D;D;D
Vest4		0.59
MVP		0.92
MPC		0.67
ClinPred		0.92	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.73

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

Other links and lift over

dbSNP: rs199893357; hg19: chr11-47360169;