16-15737461-G-T

Variant names:

• chr16-15737461-G-T
• rs534384552
• NM_002474.3:c.3281C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002474.3(MYH11):​c.3281C>A​(p.Ala1094Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,548 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20176962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.3281C>A	p.Ala1094Glu	missense_variant	Exon 25 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.3302C>A	p.Ala1101Glu	missense_variant	Exon 26 of 43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.3302C>A	p.Ala1101Glu	missense_variant	Exon 26 of 42		NP_001035203.1
MYH11	NM_022844.3	c.3281C>A	p.Ala1094Glu	missense_variant	Exon 25 of 42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.3281C>A	p.Ala1094Glu	missense_variant	Exon 25 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.3302C>A	p.Ala1101Glu	missense_variant	Exon 26 of 43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250688 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135600

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: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460548 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726658

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: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.0080	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	.;.;.;T
Eigen	Benign	-0.034
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.1	.;.;M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.3	N;N;.;N
REVEL	Benign	0.22
Sift	Benign	0.25	T;T;.;T
Sift4G	Benign	0.78	T;T;T;T
Polyphen		0.030	.;.;.;B
Vest4		0.25
MutPred		0.41		.;.;Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP		0.58
MPC		0.22
ClinPred		0.38	T
GERP RS		4.5
Varity_R		0.34
gMVP		0.34

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: rs534384552; hg19: chr16-15831318;