dbSNP rs373012629: MYBPC3:c.3191-7C>T (chr11-47333340-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000256.3(MYBPC3):c.3191-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,410,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

MYBPC3
NM_000256.3 splice_region, intron

Scores

Splicing: ADA: 0.0001342

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:4

Conservation

PhyloP100: 1.10

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-47333340-G-A is Benign according to our data. Variant chr11-47333340-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 304947.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=4}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC3	NM_000256.3 link	c.3191-7C>T		splice_region_variant, intron_variant	Intron 29 of 34	ENST00000545968.6	NP_000247.2	Q14896-1A5YM48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC3	ENST00000545968.6 link	c.3191-7C>T		splice_region_variant, intron_variant	Intron 29 of 34	5	NM_000256.3	ENSP00000442795.1		Q14896-1
MYBPC3	ENST00000399249.6 link	c.3191-7C>T		splice_region_variant, intron_variant	Intron 28 of 33	5		ENSP00000382193.2		A8MXZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000550

AC:

AN:

181902

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

97716

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:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1410228

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

696068

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:

0.0000535

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000684

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy

Uncertain:1Benign:2

Sep 12, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 09, 2023

All of Us Research Program, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiomyopathy

Uncertain:1Benign:1

Dec 16, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated Cardiomyopathy, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Left ventricular noncompaction cardiomyopathy

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Apr 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.010

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