20-36548163-G-T

Variant names:

• chr20-36548163-G-T
• rs573813643
• NM_006097.5:c.316G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006097.5(MYL9):​c.316G>T​(p.Ala106Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A106T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL9 NM_006097.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.95
• Publications: 1 publications found

Genes affected

MYL9 (HGNC:15754): (myosin light chain 9) Myosin, a structural component of muscle, consists of two heavy chains and four light chains. The protein encoded by this gene is a myosin light chain that may regulate muscle contraction by modulating the ATPase activity of myosin heads. The encoded protein binds calcium and is activated by myosin light chain kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLGAP4-AS1 (HGNC:51223): (DLGAP4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006097.5. 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
	MYL9	NM_006097.5	MANE Select	c.316G>T	p.Ala106Ser	missense	Exon 3 of 4	NP_006088.2
	MYL9	NM_181526.3		c.185-914G>T		intron	N/A	NP_852667.1	P24844-2
	DLGAP4-AS1	NR_109939.1		n.467+23278C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL9	ENST00000279022.7	TSL:1 MANE Select	c.316G>T	p.Ala106Ser	missense	Exon 3 of 4	ENSP00000279022.2	P24844-1
	MYL9	ENST00000346786.2	TSL:1	c.185-914G>T		intron	N/A	ENSP00000217313.2	P24844-2
	DLGAP4-AS1	ENST00000439595.5	TSL:1	n.467+23278C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		9.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.84	P
Vest4		0.76
MutPred		0.75		Gain of phosphorylation at A106 (P = 0.0652)
MVP		0.87
MPC		1.3
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.40
gMVP		0.86
Mutation Taster		=26/74	disease causing

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: rs573813643; hg19: chr20-35176566; COSMIC: COSV54073200;