chr20-36545018-G-C

Variant names:

• chr20-36545018-G-C
• NM_006097.5:c.134G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006097.5(MYL9):​c.134G>C​(p.Arg45Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYL9 NM_006097.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL9	NM_006097.5	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 4	ENST00000279022.7	NP_006088.2
MYL9	NM_181526.3	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 3		NP_852667.1
DLGAP4-AS1	NR_109939.1	n.467+26423C>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL9	ENST00000279022.7	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 4	1	NM_006097.5	ENSP00000279022.2
MYL9	ENST00000346786.2	c.134G>C	p.Arg45Pro	missense_variant	Exon 2 of 3	1		ENSP00000217313.2
DLGAP4-AS1	ENST00000439595.5	n.467+26423C>G		intron_variant	Intron 2 of 4	1
DLGAP4-AS1	ENST00000425233.6	n.580-17094C>G		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.8	H;H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.99	D;.
Vest4		0.82
MutPred		0.50		Gain of disorder (P = 0.1);Gain of disorder (P = 0.1);
MVP		0.86
MPC		1.0
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.91
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-35173421;