rs34287137

Variant names:

• chr16-15748148-G-A
• rs34287137
• NM_002474.3:c.2079C>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.2079C>T​(p.Phe693Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,896 control chromosomes in the GnomAD database, including 1,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (892 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (758 hom.)
• Consequence: MYH11 NM_002474.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.462
• Publications: 4 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=-0.79).
• BP6: Variant 16-15748148-G-A is Benign according to our data. Variant chr16-15748148-G-A is described in ClinVar as Benign. ClinVar VariationId is 138329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.462 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 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.2079C>T	p.Phe693Phe	synonymous	Exon 17 of 41	NP_002465.1	P35749-1
	MYH11	NM_001040113.2	MANE Plus Clinical	c.2100C>T	p.Phe700Phe	synonymous	Exon 18 of 43	NP_001035202.1	P35749-3
	MYH11	NM_001040114.2		c.2100C>T	p.Phe700Phe	synonymous	Exon 18 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.2079C>T	p.Phe693Phe	synonymous	Exon 17 of 41	ENSP00000300036.5	P35749-1
	MYH11	ENST00000452625.7	TSL:1 MANE Plus Clinical	c.2100C>T	p.Phe700Phe	synonymous	Exon 18 of 43	ENSP00000407821.2	P35749-3
	MYH11	ENST00000396324.7	TSL:1	c.2100C>T	p.Phe700Phe	synonymous	Exon 18 of 42	ENSP00000379616.3	P35749-2

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8869 AN: 152124 Hom.: 887 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0425

GnomAD2 exomes AF: 0.0165 AC: 4133 AN: 250988 AF XY: 0.0124

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000840

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00668 AC: 9771 AN: 1461654 Hom.: 758 Cov.: 34 AF XY: 0.00587 AC XY: 4268 AN XY: 727136

African (AFR) AF: 0.209 AC: 6994 AN: 33478

American (AMR) AF: 0.0141 AC: 632 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00367 AC: 96 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000441 AC: 38 AN: 86258

European-Finnish (FIN) AF: 0.000903 AC: 48 AN: 53182

Middle Eastern (MID) AF: 0.0182 AC: 105 AN: 5768

European-Non Finnish (NFE) AF: 0.000857 AC: 953 AN: 1112012

Other (OTH) AF: 0.0150 AC: 904 AN: 60396

GnomAD4 genome AF: 0.0584 AC: 8894 AN: 152242 Hom.: 892 Cov.: 32 AF XY: 0.0569 AC XY: 4233 AN XY: 74442

African (AFR) AF: 0.202 AC: 8379 AN: 41508

American (AMR) AF: 0.0217 AC: 332 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68016

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0344 Hom.: 373

Bravo AF: 0.0662

Asia WGS AF: 0.0140 AC: 50 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Familial thoracic aortic aneurysm and aortic dissection (3)
-	-	2	Aortic aneurysm, familial thoracic 4 (2)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.78
DANN	Benign	0.69
PhyloP100		-0.46
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34287137; hg19: chr16-15842005; COSMIC: COSV55546844;