rs149213047

Variant names:

• chr12-101629446-T-A
• rs149213047
• NM_002465.4:c.191T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-101629446-T-A
• chr12-101629446-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002465.4(MYBPC1):​c.191T>A​(p.Val64Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V64A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPC1 NM_002465.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.61
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• arthrogryposis, distal, type 1B

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• myopathy, congenital, with tremor

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• lethal congenital contracture syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lethal congenital contracture syndrome 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14876422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPC1	NM_002465.4	c.191T>A	p.Val64Asp	missense_variant	Exon 6 of 32	ENST00000361466.7	NP_002456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPC1	ENST00000361466.7	c.191T>A	p.Val64Asp	missense_variant	Exon 6 of 32	1	NM_002465.4	ENSP00000354849.2
MYBPC1	ENST00000551300.5	c.-182T>A		5_prime_UTR_variant	Exon 7 of 32	1		ENSP00000447116.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.63
DEOGEN2	Benign	0.0095	.;.;.;.;.;T;.;.;.;.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;N;N;N;.;.;N
PhyloP100		6.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.51	N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.085	T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.016	.;.;.;.;B;B;B;.;.;.;.;B
Vest4		0.40
MutPred		0.37		.;.;.;.;.;Gain of catalytic residue at P55 (P = 0.0016);.;.;.;.;.;.;
MVP		0.21
MPC		0.063
ClinPred		0.40	T
GERP RS		5.3
Varity_R		0.26
gMVP		0.37
Mutation Taster		=286/14	polymorphism

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

Other links and lift over

dbSNP: rs149213047; hg19: chr12-102023224;