chr16-15724166-C-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_002474.3(MYH11):c.4360G>C(p.Asp1454His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MYH11
NM_002474.3 missense
NM_002474.3 missense
Scores
16
2
1
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]
NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.968
PP5
Variant 16-15724166-C-G is Pathogenic according to our data. Variant chr16-15724166-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374162.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.4360G>C | p.Asp1454His | missense_variant | 31/41 | ENST00000300036.6 | NP_002465.1 | |
MYH11 | NM_001040113.2 | c.4381G>C | p.Asp1461His | missense_variant | 32/43 | ENST00000452625.7 | NP_001035202.1 | |
NDE1 | NM_017668.3 | c.948-25C>G | intron_variant | ENST00000396354.6 | NP_060138.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4360G>C | p.Asp1454His | missense_variant | 31/41 | 1 | NM_002474.3 | ENSP00000300036.5 | ||
MYH11 | ENST00000452625.7 | c.4381G>C | p.Asp1461His | missense_variant | 32/43 | 1 | NM_001040113.2 | ENSP00000407821.2 | ||
NDE1 | ENST00000396354.6 | c.948-25C>G | intron_variant | 1 | NM_017668.3 | ENSP00000379642.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitral regurgitation;C0027092:Myopia;C0040961:Tricuspid regurgitation;C0344905:Abnormal left ventricle morphology;C1298820:Aortic root aneurysm Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Sep 12, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;.;H;H
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
MutPred
0.83
.;.;Loss of ubiquitination at K1449 (P = 0.0245);Loss of ubiquitination at K1449 (P = 0.0245);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at