Genetic Variant MYOG:p.Gly153Arg (chr1-203085505-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002479.6(MYOG):c.457G>A(p.Gly153Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,612,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

MYOG
NM_002479.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.889

Publications

1 publications found

Variant links:

Genes affected

MYOG (HGNC:7612): (myogenin) Myogenin is a muscle-specific transcription factor that can induce myogenesis in a variety of cell types in tissue culture. It is a member of a large family of proteins related by sequence homology, the helix-loop-helix (HLH) proteins. It is essential for the development of functional skeletal muscle. [provided by RefSeq, Jul 2008]

MYOG links:

MYOPARR (HGNC:54178): (myogenin promoter associated myogenic regulatory antisense long non coding RNA) Predicted to enable RNA polymerase II core promoter sequence-specific DNA binding activity. Predicted to be involved in myoblast fate specification. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to act upstream of or within protein-containing complex assembly and skeletal muscle fiber development. [provided by Alliance of Genome Resources, Apr 2022]

MYOPARR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060824394).

BS2

High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002479.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOG	NM_002479.6	MANE Select	c.457G>A	p.Gly153Arg	missense	Exon 1 of 3	NP_002470.2
	MYOPARR	NR_160550.1		n.387+932C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOG	ENST00000241651.5	TSL:1 MANE Select	c.457G>A	p.Gly153Arg	missense	Exon 1 of 3	ENSP00000241651.4	P15173
MYOG	ENST00000944760.1		c.457G>A	p.Gly153Arg	missense	Exon 1 of 3	ENSP00000614819.1
MYOG	ENST00000944761.1		c.457G>A	p.Gly153Arg	missense	Exon 1 of 3	ENSP00000614820.1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000941

AC:

AN:

244300

AF XY:

0.0000677

show subpopulations

Gnomad AFR exome

AF:

0.000869

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000549

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1459884

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33454

American (AMR)

AF:

0.0000448

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26008

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39676

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1110874

Other (OTH)

AF:

0.0000664

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41584

American (AMR)

AF:

0.0000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-0.025

Eigen_PC

Benign

-0.0024

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.061

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

1.4

PhyloP100

0.89

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.50

REVEL

Uncertain

0.39

Sift

Benign

0.26

Sift4G

Benign

0.46

Polyphen

0.88

Vest4

0.32

MutPred

0.28

Gain of methylation at G153 (P = 0.038)

MVP

0.72

MPC

0.89

ClinPred

0.055

GERP RS

4.8

Varity_R

0.084

gMVP

0.30

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over