chr12-101614502-A-G

Position:

• chr12-101614502-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002465.4(MYBPC1):​c.32A>G​(p.Glu11Gly) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYBPC1 NM_002465.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.11

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]

LOC105369938 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.340496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPC1	NM_002465.4	c.32A>G	p.Glu11Gly	missense_variant	2/32	ENST00000361466.7
LOC105369938	XR_001749279.2	n.722+52T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPC1	ENST00000361466.7	c.32A>G	p.Glu11Gly	missense_variant	2/32	1	NM_002465.4	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Lethal congenital contracture syndrome 4 Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	.;.;.;T;.;.;.;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.67	T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.34	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N;.;N;.;N;N;N;N;N
MutationTaster	Benign	0.85	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.46	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;T;D;D;D;D;D;D;D
Sift4G	Benign	0.13	T;T;T;T;T;T;T;T;T
Polyphen		0.99, 0.089, 0.98	.;.;D;B;D;.;.;.;D
Vest4		0.51
MutPred		0.23		Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);Gain of catalytic residue at V12 (P = 0.0399);
MVP		0.40
MPC		0.051
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs1309691397; hg19: chr12-102008280;