rs11570105

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000256.3(MYBPC3):c.2603-11C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,476,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

MYBPC3
NM_000256.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008853

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0380

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-47336022-G-A is Benign according to our data. Variant chr11-47336022-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC3	NM_000256.3 linkuse as main transcript	c.2603-11C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000545968.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MYBPC3	ENST00000545968.6 linkuse as main transcript	c.2603-11C>T	splice_polypyrimidine_tract_variant, intron_variant	5	NM_000256.3	P4	Q14896-1
MYBPC3	ENST00000399249.6 linkuse as main transcript	c.2603-11C>T	splice_polypyrimidine_tract_variant, intron_variant	5		A2
MYBPC3	ENST00000544791.1 linkuse as main transcript	c.*108-11C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

142468

Hom.:

AF XY:

0.0000391

AC XY:

AN XY:

76730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000573

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1323824

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

646790

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000566

Gnomad4 OTH exome

AF:

0.0000184

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Mar 26, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Jun 26, 2023	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 18, 2014

c.2603-11C>T in intron 25 of MYBPC3: This variant is not expected to have clinic al significance because a C>T change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. -

Cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Mar 08, 2019

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

Cadd

Benign

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000089

dbscSNV1_RF

Benign

0.0040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over