20-36549240-A-C

Position:

• chr20-36549240-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006097.5(MYL9):​c.510A>C​(p.Lys170Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL9 NM_006097.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0750

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL9	NM_006097.5	c.510A>C	p.Lys170Asn	missense_variant	4/4	ENST00000279022.7	NP_006088.2
MYL9	NM_181526.3	c.348A>C	p.Lys116Asn	missense_variant	3/3		NP_852667.1
DLGAP4-AS1	NR_109939.1	n.467+22201T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL9	ENST00000279022.7	c.510A>C	p.Lys170Asn	missense_variant	4/4	1	NM_006097.5	ENSP00000279022.2
MYL9	ENST00000346786.2	c.348A>C	p.Lys116Asn	missense_variant	3/3	1		ENSP00000217313.2
DLGAP4-AS1	ENST00000439595.5	n.467+22201T>G		intron_variant		1
DLGAP4-AS1	ENST00000425233.6	n.580-21316T>G		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

Aug 04, 2021

The c.510A>C (p.K170N) alteration is located in exon 4 (coding exon 3) of the MYL9 gene. This alteration results from a A to C substitution at nucleotide position 510, causing the lysine (K) at amino acid position 170 to be replaced by an asparagine (N). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.42	T;T
MetaSVM	Uncertain	-0.084	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.0050	B;.
Vest4		0.63
MutPred		0.27		Loss of ubiquitination at K170 (P = 0.0255);.;
MVP		0.60
MPC		0.74
ClinPred		0.94	D
GERP RS		-6.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.29
gMVP		0.80

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: chr20-35177643;