rs763514919

Variant names:

• chr16-15741494-G-A
• rs763514919
• NM_002474.3:c.2828C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-15741494-G-A
• chr16-15741494-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002474.3(MYH11):​c.2828C>T​(p.Ala943Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,592 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A943D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63
• Publications: 0 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 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
• visceral myopathy 2

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

ENSG00000263065 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15505409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.2828C>T	p.Ala943Val	missense_variant	Exon 22 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.2849C>T	p.Ala950Val	missense_variant	Exon 23 of 43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.2849C>T	p.Ala950Val	missense_variant	Exon 23 of 42		NP_001035203.1
MYH11	NM_022844.3	c.2828C>T	p.Ala943Val	missense_variant	Exon 22 of 42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.2828C>T	p.Ala943Val	missense_variant	Exon 22 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.2849C>T	p.Ala950Val	missense_variant	Exon 23 of 43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456592 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724886

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111976

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	.;.;.;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	1.9	.;.;L;L
PhyloP100		3.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.5	N;N;.;N
REVEL	Uncertain	0.40
Sift	Benign	0.16	T;T;.;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.0	.;.;.;B
Vest4		0.11
MutPred		0.27		.;.;Gain of MoRF binding (P = 0.085);Gain of MoRF binding (P = 0.085);
MVP		0.74
MPC		0.17
ClinPred		0.62	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.10
Mutation Taster		=98/2	polymorphism

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: rs763514919; hg19: chr16-15835351; COSMIC: COSV55552214; COSMIC: COSV55552214;