rs397514444

Variant names:

• chr11-47332267-AAGGTAAAGAGAGGGAGGGAAGCCAT-A
• rs397514444
• NM_000256.3:c.3628-34_3628-10delATGGCTTCCCTCCCTCTCTTTACCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000256.3(MYBPC3):​c.3628-34_3628-10delATGGCTTCCCTCCCTCTCTTTACCT variant causes a intron 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 risk factor (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYBPC3 NM_000256.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.16

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 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.3628-34_3628-10delATGGCTTCCCTCCCTCTCTTTACCT		intron_variant	Intron 32 of 34	ENST00000545968.6	NP_000247.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6	c.3628-34_3628-10delATGGCTTCCCTCCCTCTCTTTACCT		intron_variant	Intron 32 of 34	5	NM_000256.3	ENSP00000442795.1
MYBPC3	ENST00000399249.6	c.3628-34_3628-10delATGGCTTCCCTCCCTCTCTTTACCT		intron_variant	Intron 31 of 33	5		ENSP00000382193.2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Cardiomyopathy, familial hypertrophic, 4, susceptibility to Other:1

Feb 01, 2009

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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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: rs397514444; hg19: chr11-47353818;