16-15823340-G-A

Variant names:

• chr16-15823340-G-A
• rs1050111
• NM_002474.3:c.417C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002474.3(MYH11):​c.417C>T​(p.Val139Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,076 control chromosomes in the GnomAD database, including 9,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V139V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.10 (865 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8929 hom.)
• Consequence: MYH11 NM_002474.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.874
• Publications: 14 publications found

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]

MYH11 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• aortic aneurysm, familial thoracic 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• megacystis-microcolon-intestinal hypoperistalsis syndrome 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• visceral myopathy 2

  Inheritance: AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 16-15823340-G-A is Benign according to our data. Variant chr16-15823340-G-A is described in ClinVar as Benign. ClinVar VariationId is 138366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.874 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002474.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH11	NM_002474.3	MANE Select	c.417C>T	p.Val139Val	synonymous	Exon 3 of 41	NP_002465.1	P35749-1
	MYH11	NM_001040113.2	MANE Plus Clinical	c.417C>T	p.Val139Val	synonymous	Exon 3 of 43	NP_001035202.1	P35749-3
	MYH11	NM_001040114.2		c.417C>T	p.Val139Val	synonymous	Exon 3 of 42	NP_001035203.1	P35749-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH11	ENST00000300036.6	TSL:1 MANE Select	c.417C>T	p.Val139Val	synonymous	Exon 3 of 41	ENSP00000300036.5	P35749-1
	MYH11	ENST00000452625.7	TSL:1 MANE Plus Clinical	c.417C>T	p.Val139Val	synonymous	Exon 3 of 43	ENSP00000407821.2	P35749-3
	MYH11	ENST00000396324.7	TSL:1	c.417C>T	p.Val139Val	synonymous	Exon 3 of 42	ENSP00000379616.3	P35749-2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15662 AN: 152090 Hom.: 864 Cov.: 33

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.0994 AC: 24992 AN: 251486 AF XY: 0.0993

Gnomad AFR exome AF: 0.0869

Gnomad AMR exome AF: 0.0691

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0946

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.108 AC: 157475 AN: 1461868 Hom.: 8929 Cov.: 34 AF XY: 0.107 AC XY: 77872 AN XY: 727244

African (AFR) AF: 0.0846 AC: 2831 AN: 33478

American (AMR) AF: 0.0690 AC: 3088 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3794 AN: 26136

East Asian (EAS) AF: 0.0651 AC: 2586 AN: 39700

South Asian (SAS) AF: 0.0625 AC: 5387 AN: 86256

European-Finnish (FIN) AF: 0.105 AC: 5595 AN: 53418

Middle Eastern (MID) AF: 0.134 AC: 774 AN: 5768

European-Non Finnish (NFE) AF: 0.114 AC: 127006 AN: 1111996

Other (OTH) AF: 0.106 AC: 6414 AN: 60394

GnomAD4 genome AF: 0.103 AC: 15675 AN: 152208 Hom.: 865 Cov.: 33 AF XY: 0.102 AC XY: 7594 AN XY: 74398

African (AFR) AF: 0.0848 AC: 3525 AN: 41550

American (AMR) AF: 0.0944 AC: 1442 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3468

East Asian (EAS) AF: 0.0834 AC: 431 AN: 5170

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8034 AN: 67996

Other (OTH) AF: 0.110 AC: 233 AN: 2116

Alfa AF: 0.110 Hom.: 678

Bravo AF: 0.101

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.121

EpiControl AF: 0.121

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Familial thoracic aortic aneurysm and aortic dissection (4)
-	-	4	not specified (4)
-	-	2	Aortic aneurysm, familial thoracic 4 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.2
DANN	Benign	0.86
PhyloP100		-0.87
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050111; hg19: chr16-15917197; COSMIC: COSV55551037;