16-15740090-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002474.3(MYH11):​c.2958G>T​(p.Glu986Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MYH11
NM_002474.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.370
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036756337).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYH11NM_002474.3 linkc.2958G>T p.Glu986Asp missense_variant 23/41 ENST00000300036.6 NP_002465.1 P35749-1A0A024QZJ4
MYH11NM_001040113.2 linkc.2979G>T p.Glu993Asp missense_variant 24/43 ENST00000452625.7 NP_001035202.1 P35749-3
MYH11NM_001040114.2 linkc.2979G>T p.Glu993Asp missense_variant 24/42 NP_001035203.1 P35749-2
MYH11NM_022844.3 linkc.2958G>T p.Glu986Asp missense_variant 23/42 NP_074035.1 P35749-4A0A024QZJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYH11ENST00000300036.6 linkc.2958G>T p.Glu986Asp missense_variant 23/411 NM_002474.3 ENSP00000300036.5 P35749-1
MYH11ENST00000452625.7 linkc.2979G>T p.Glu993Asp missense_variant 24/431 NM_001040113.2 ENSP00000407821.2 P35749-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251492
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.052
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
3.8
DANN
Benign
0.81
DEOGEN2
Benign
0.30
.;.;.;T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.74
T;T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.037
T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
-0.34
.;.;N;N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
1.8
N;N;.;N
REVEL
Benign
0.21
Sift
Benign
1.0
T;T;.;T
Sift4G
Benign
0.67
T;T;T;T
Polyphen
0.0
.;.;.;B
Vest4
0.10
MutPred
0.28
.;.;Loss of ubiquitination at K981 (P = 0.1576);Loss of ubiquitination at K981 (P = 0.1576);
MVP
0.40
MPC
0.16
ClinPred
0.037
T
GERP RS
-5.8
Varity_R
0.052
gMVP
0.16

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774274573; hg19: chr16-15833947; API