Variant chr20-36549241-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000279022.7(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
ENST00000279022.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89

Variant links:

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]

MYL9 links:

DLGAP4-AS1 (HGNC:51223): (DLGAP4 antisense RNA 1)

DLGAP4-AS1 links:

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ACMG classification

Classification made for transcript

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
MYL9	NM_006097.5 linkuse as main transcript	c.511G>C	p.Asp171His	missense_variant	4/4	ENST00000279022.7	NP_006088.2
DLGAP4-AS1	NR_109939.1 linkuse as main transcript	n.467+22200C>G		intron_variant, non_coding_transcript_variant
MYL9	NM_181526.3 linkuse as main transcript	c.349G>C	p.Asp117His	missense_variant	3/3		NP_852667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL9	ENST00000279022.7 linkuse as main transcript	c.511G>C	p.Asp171His	missense_variant	4/4	1	NM_006097.5	ENSP00000279022	P1	P24844-1
MYL9	ENST00000346786.2 linkuse as main transcript	c.349G>C	p.Asp117His	missense_variant	3/3	1		ENSP00000217313		P24844-2
DLGAP4-AS1	ENST00000425233.6 linkuse as main transcript	n.580-21317C>G		intron_variant, non_coding_transcript_variant		5
DLGAP4-AS1	ENST00000439595.5 linkuse as main transcript	n.467+22200C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459336

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725926

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

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

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over