20-36549091-G-T

Position:

• chr20-36549091-G-T

Variant summary

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

The NM_006097.5(MYL9):​c.361G>T​(p.Asp121Tyr) 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. 12/21 in silico tools predict a damaging 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: MYL9 NM_006097.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.95

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:):

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, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL9	NM_006097.5	c.361G>T	p.Asp121Tyr	missense_variant	4/4	ENST00000279022.7	NP_006088.2
MYL9	NM_181526.3	c.199G>T	p.Asp67Tyr	missense_variant	3/3		NP_852667.1
DLGAP4-AS1	NR_109939.1	n.467+22350C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL9	ENST00000279022.7	c.361G>T	p.Asp121Tyr	missense_variant	4/4	1	NM_006097.5	ENSP00000279022.2
MYL9	ENST00000346786.2	c.199G>T	p.Asp67Tyr	missense_variant	3/3	1		ENSP00000217313.2
DLGAP4-AS1	ENST00000439595.5	n.467+22350C>A		intron_variant		1
DLGAP4-AS1	ENST00000425233.6	n.580-21167C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 04, 2024

The c.361G>T (p.D121Y) alteration is located in exon 4 (coding exon 3) of the MYL9 gene. This alteration results from a G to T substitution at nucleotide position 361, causing the aspartic acid (D) at amino acid position 121 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Pathogenic	0.74
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.63	P;.
Vest4		0.75
MutPred		0.36		Loss of catalytic residue at D121 (P = 0.0121);.;
MVP		0.88
MPC		1.6
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.93
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-35177494;