16-15741822-T-C

Position:

• chr16-15741822-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002474.3(MYH11):​c.2590A>G​(p.Thr864Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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]

ENSG00000263065 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103812575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_002474.3	c.2590A>G	p.Thr864Ala	missense_variant	21/41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.2611A>G	p.Thr871Ala	missense_variant	22/43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.2611A>G	p.Thr871Ala	missense_variant	22/42		NP_001035203.1
MYH11	NM_022844.3	c.2590A>G	p.Thr864Ala	missense_variant	21/42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.2590A>G	p.Thr864Ala	missense_variant	21/41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.2611A>G	p.Thr871Ala	missense_variant	22/43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	.;.;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.57	.;.;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.12	N;N;.;N
REVEL	Benign	0.079
Sift	Benign	0.20	T;T;.;T
Sift4G	Benign	0.47	T;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.25
MutPred		0.46		.;.;Loss of phosphorylation at T864 (P = 0.0264);Loss of phosphorylation at T864 (P = 0.0264);
MVP		0.40
MPC		0.74
ClinPred		0.16	T
GERP RS		4.0
Varity_R		0.054
gMVP		0.13

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

Other links and lift over

dbSNP: rs1801902; hg19: chr16-15835679;