16-15737585-G-T

Variant names:

• chr16-15737585-G-T
• rs12149651
• NM_002474.3:c.3157C>A

Variant summary

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

The NM_002474.3(MYH11):​c.3157C>A​(p.Leu1053Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,310 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: 6.8e-7 (0 hom.)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69

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=0.31400603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.3157C>A	p.Leu1053Met	missense_variant	Exon 25 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.3178C>A	p.Leu1060Met	missense_variant	Exon 26 of 43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.3178C>A	p.Leu1060Met	missense_variant	Exon 26 of 42		NP_001035203.1
MYH11	NM_022844.3	c.3157C>A	p.Leu1053Met	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.3157C>A	p.Leu1053Met	missense_variant	Exon 25 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.3178C>A	p.Leu1060Met	missense_variant	Exon 26 of 43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461310 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726994

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	.;.;.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.8	.;.;L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.0	N;N;.;N
REVEL	Uncertain	0.41
Sift	Benign	0.046	D;D;.;D
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.76	.;.;.;P
Vest4		0.38
MutPred		0.42		.;.;Gain of methylation at K1057 (P = 0.0717);Gain of methylation at K1057 (P = 0.0717);
MVP		0.71
MPC		0.21
ClinPred		0.89	D
GERP RS		4.6
Varity_R		0.29
gMVP		0.23

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: rs12149651; hg19: chr16-15831442;