rs3817552
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002465.4(MYBPC1):āc.1518C>Gā(p.His506Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,664 control chromosomes in the GnomAD database, including 20,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.15 ( 1815 hom., cov: 32)
Exomes š: 0.16 ( 19143 hom. )
Consequence
MYBPC1
NM_002465.4 missense
NM_002465.4 missense
Scores
3
6
7
Clinical Significance
Conservation
PhyloP100: 2.45
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0017406046).
BP6
?
Variant 12-101651385-C-G is Benign according to our data. Variant chr12-101651385-C-G is described in ClinVar as [Benign]. Clinvar id is 129642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-101651385-C-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC1 | NM_002465.4 | c.1518C>G | p.His506Gln | missense_variant | 16/32 | ENST00000361466.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC1 | ENST00000361466.7 | c.1518C>G | p.His506Gln | missense_variant | 16/32 | 1 | NM_002465.4 | A2 | |
ENST00000547027.1 | n.258-4357G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.148 AC: 22569AN: 151980Hom.: 1814 Cov.: 32
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GnomAD3 exomes AF: 0.156 AC: 39160AN: 251400Hom.: 3474 AF XY: 0.159 AC XY: 21640AN XY: 135870
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GnomAD4 exome AF: 0.158 AC: 230827AN: 1461566Hom.: 19143 Cov.: 33 AF XY: 0.158 AC XY: 115165AN XY: 727088
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GnomAD4 genome ? AF: 0.148 AC: 22562AN: 152098Hom.: 1815 Cov.: 32 AF XY: 0.149 AC XY: 11102AN XY: 74334
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562
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593
ESP6500AA
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571
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ExAC
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19070
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Arthrogryposis, distal, type 1B Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Myopathy, congenital, with tremor Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Lethal congenital contracture syndrome 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2019 | This variant is associated with the following publications: (PMID: 17000706, 23873045) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;.;D;D;D;.;.;.;.;.;D
Vest4
MutPred
0.67
.;.;.;.;.;Gain of catalytic residue at R497 (P = 0.0011);.;.;.;.;.;.;.;
MPC
0.76
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at