rs763151112
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_002474.3(MYH11):c.598T>G(p.Ser200Ala) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 31)
Consequence
MYH11
NM_002474.3 missense
NM_002474.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 7.44
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYH11. . Gene score misZ 1.4389 (greater than the threshold 3.09). Trascript score misZ 3.4142 (greater than threshold 3.09). GenCC has associacion of gene with aortic aneurysm, familial thoracic 4, visceral myopathy 2, familial thoracic aortic aneurysm and aortic dissection, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, megacystis-microcolon-intestinal hypoperistalsis syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.3932946).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.598T>G | p.Ser200Ala | missense_variant | 5/41 | ENST00000300036.6 | NP_002465.1 | |
MYH11 | NM_001040113.2 | c.598T>G | p.Ser200Ala | missense_variant | 5/43 | ENST00000452625.7 | NP_001035202.1 | |
MYH11 | NM_001040114.2 | c.598T>G | p.Ser200Ala | missense_variant | 5/42 | NP_001035203.1 | ||
MYH11 | NM_022844.3 | c.598T>G | p.Ser200Ala | missense_variant | 5/42 | NP_074035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.598T>G | p.Ser200Ala | missense_variant | 5/41 | 1 | NM_002474.3 | ENSP00000300036.5 | ||
MYH11 | ENST00000452625.7 | c.598T>G | p.Ser200Ala | missense_variant | 5/43 | 1 | NM_001040113.2 | ENSP00000407821.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 06, 2024 | - - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 31, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH11-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 200 of the MYH11 protein (p.Ser200Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Uncertain
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;T;T
Polyphen
0.69
.;.;.;P
Vest4
MutPred
Loss of catalytic residue at S200 (P = 0.0568);Loss of catalytic residue at S200 (P = 0.0568);Loss of catalytic residue at S200 (P = 0.0568);Loss of catalytic residue at S200 (P = 0.0568);
MVP
MPC
ClinPred
D
GERP RS
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