chr16-15720220-G-T

Variant names:

• chr16-15720220-G-T
• rs780786328
• NM_002474.3:c.4884C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002474.3(MYH11):​c.4884C>A​(p.Asp1628Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 31)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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]

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20044956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.4884C>A	p.Asp1628Glu	missense_variant	Exon 34 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.4905C>A	p.Asp1635Glu	missense_variant	Exon 35 of 43	ENST00000452625.7	NP_001035202.1
NDE1	NM_017668.3	c.948-3971G>T		intron_variant	Intron 8 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.4884C>A	p.Asp1628Glu	missense_variant	Exon 34 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.4905C>A	p.Asp1635Glu	missense_variant	Exon 35 of 43	1	NM_001040113.2	ENSP00000407821.2
NDE1	ENST00000396354.6	c.948-3971G>T		intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.80
DEOGEN2	Benign	0.32	.;.;.;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.075	.;.;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.69	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.015	.;.;.;B
Vest4		0.42
MutPred		0.37		.;.;Gain of MoRF binding (P = 0.1429);Gain of MoRF binding (P = 0.1429);
MVP		0.51
MPC		0.29
ClinPred		0.18	T
GERP RS		1.4
Varity_R		0.099
gMVP		0.22

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: rs780786328; hg19: chr16-15814077;