11-47351356-T-A

Variant names:

• chr11-47351356-T-A
• NM_000256.3:c.175A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000256.3(MYBPC3):​c.175A>T​(p.Thr59Ser) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. 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: 0.159

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03483233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3	c.175A>T	p.Thr59Ser	missense_variant	Exon 2 of 35	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.175A>T	p.Thr59Ser	missense_variant	Exon 2 of 35	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.175A>T	p.Thr59Ser	missense_variant	Exon 2 of 34	5		ENSP00000382193.2
MYBPC3	ENST00000544791.1	n.175A>T		non_coding_transcript_exon_variant	Exon 2 of 27	5		ENSP00000444259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
CardioboostCm	Benign	0.0020
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.9
DANN	Benign	0.53
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.035	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.38	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.73	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.22
MutPred		0.41		Gain of disorder (P = 0.0638);Gain of disorder (P = 0.0638);Gain of disorder (P = 0.0638);
MVP		0.47
MPC		0.20
ClinPred		0.11	T
GERP RS		-2.4
Varity_R		0.14
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47372907;