20-36549241-G-C

Variant names:

• chr20-36549241-G-C
• NM_006097.5:c.511G>C

Variant summary

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

The NM_006097.5(MYL9):​c.511G>C​(p.Asp171His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,336 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYL9 NM_006097.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.89

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL9	NM_006097.5	c.511G>C	p.Asp171His	missense_variant	Exon 4 of 4	ENST00000279022.7	NP_006088.2
MYL9	NM_181526.3	c.349G>C	p.Asp117His	missense_variant	Exon 3 of 3		NP_852667.1
DLGAP4-AS1	NR_109939.1	n.467+22200C>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL9	ENST00000279022.7	c.511G>C	p.Asp171His	missense_variant	Exon 4 of 4	1	NM_006097.5	ENSP00000279022.2
MYL9	ENST00000346786.2	c.349G>C	p.Asp117His	missense_variant	Exon 3 of 3	1		ENSP00000217313.2
DLGAP4-AS1	ENST00000439595.5	n.467+22200C>G		intron_variant	Intron 2 of 4	1
DLGAP4-AS1	ENST00000425233.6	n.580-21317C>G		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459336 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725926

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511G>C (p.D171H) alteration is located in exon 4 (coding exon 3) of the MYL9 gene. This alteration results from a G to C substitution at nucleotide position 511, causing the aspartic acid (D) at amino acid position 171 to be replaced by a histidine (H). 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	0.66
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.99	D;.
Vest4		0.71
MutPred		0.40		Gain of MoRF binding (P = 0.0428);.;
MVP		0.82
MPC		1.3
ClinPred		0.98	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.52
gMVP		0.69

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: chr20-35177644;