rs769022373

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP3BS1_Supporting

The NM_002465.4(MYBPC1):c.2572C>T(p.Arg858Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,948 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

MYBPC1
NM_002465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

Variant links:

Genes affected

MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

MYBPC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000123 (18/1461778) while in subpopulation AMR AF= 0.000112 (5/44722). AF 95% confidence interval is 0.0000436. There are 1 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC1	NM_002465.4 link	c.2572C>T	p.Arg858Cys	missense_variant	Exon 24 of 32	ENST00000361466.7	NP_002456.2	Q00872-4Q86TA8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7 link	c.2572C>T	p.Arg858Cys	missense_variant	Exon 24 of 32	1	NM_002465.4	ENSP00000354849.2		Q00872-4
MYBPC1	ENST00000551300.5 link	c.2200C>T	p.Arg734Cys	missense_variant	Exon 25 of 32	1		ENSP00000447116.1		G3V1V7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251420

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

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:

0.0000294

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Oct 23, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.091

.;.;.;.;.;T;.;.;.;.;.;.;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.80

D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.2

.;M;.;.;.;.;.;.;.;.;.;.;M

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.6

D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.027

D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

0.91, 1.0

.;.;.;.;P;.;D;.;.;.;.;.;D

Vest4

0.80

MutPred

0.62

.;Loss of MoRF binding (P = 0.0031);.;.;.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0031);

MVP

0.73

MPC

0.87

ClinPred

0.98

GERP RS

5.8

Varity_R

0.32

gMVP

0.80

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

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