rs776016983

Variant names:

• chr16-15717248-C-A
• rs776016983
• NM_002474.3:c.5396G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-15717248-C-A
• chr16-15717248-C-G
• chr16-15717248-C-T

Variant summary

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

The NM_002474.3(MYH11):​c.5396G>T​(p.Ser1799Ile) 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. 12/21 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: 32)
• Consequence: MYH11 NM_002474.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2966782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.5396G>T	p.Ser1799Ile	missense_variant	Exon 38 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.5417G>T	p.Ser1806Ile	missense_variant	Exon 39 of 43	ENST00000452625.7	NP_001035202.1
NDE1	NM_017668.3	c.948-6943C>A		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.5396G>T	p.Ser1799Ile	missense_variant	Exon 38 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.5417G>T	p.Ser1806Ile	missense_variant	Exon 39 of 43	1	NM_001040113.2	ENSP00000407821.2
NDE1	ENST00000396354.6	c.948-6943C>A		intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.48	.;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.090	.;.;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N;N;.;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.029	D;D;.;D
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.048	.;.;.;B
Vest4		0.54
MutPred		0.35		.;.;Loss of phosphorylation at S1799 (P = 0.038);Loss of phosphorylation at S1799 (P = 0.038);
MVP		0.64
MPC		0.24
ClinPred		0.86	D
GERP RS		4.3
Varity_R		0.36
gMVP		0.32

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: rs776016983; hg19: chr16-15811105;