rs573813643

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-36548163-G-A
• chr20-36548163-G-C
• chr20-36548163-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006097.5(MYL9):​c.316G>A​(p.Ala106Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: MYL9 NM_006097.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

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>A	p.Ala106Thr	missense	Exon 3 of 4	NP_006088.2
	MYL9	NM_181526.3		c.185-914G>A		intron	N/A	NP_852667.1	P24844-2
	DLGAP4-AS1	NR_109939.1		n.467+23278C>T		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>A	p.Ala106Thr	missense	Exon 3 of 4	ENSP00000279022.2	P24844-1
	MYL9	ENST00000346786.2	TSL:1	c.185-914G>A		intron	N/A	ENSP00000217313.2	P24844-2
	DLGAP4-AS1	ENST00000439595.5	TSL:1	n.467+23278C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 249452 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1460998 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726802

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111464

Other (OTH) AF: 0.0000331 AC: 2 AN: 60348

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		9.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.8	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.86	P
Vest4		0.85
MutPred		0.76		Gain of phosphorylation at A106 (P = 0.0652)
MVP		0.91
MPC		1.2
ClinPred		0.78	D
GERP RS		4.9
Varity_R		0.69
gMVP		0.91
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: COSV99640962;