16-15771585-G-C

Position:

• chr16-15771585-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002474.3(MYH11):​c.1017C>G​(p.Ser339Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37308866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_002474.3	c.1017C>G	p.Ser339Arg	missense_variant	9/41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.1038C>G	p.Ser346Arg	missense_variant	10/43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.1038C>G	p.Ser346Arg	missense_variant	10/42		NP_001035203.1
MYH11	NM_022844.3	c.1017C>G	p.Ser339Arg	missense_variant	9/42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.1017C>G	p.Ser339Arg	missense_variant	9/41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.1038C>G	p.Ser346Arg	missense_variant	10/43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	5.2
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.87	.;.;.;D
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.042	N
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.3	.;.;M;M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.5	D;D;.;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0060	D;D;.;D
Sift4G	Uncertain	0.039	D;T;T;T
Polyphen		0.59	.;.;.;P
Vest4		0.30
MutPred		0.50		.;.;Loss of phosphorylation at S339 (P = 0.0678);Loss of phosphorylation at S339 (P = 0.0678);
MVP		0.70
MPC		0.95
ClinPred		0.78	D
GERP RS		-3.6
Varity_R		0.25
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs112161189; hg19: chr16-15865442;