Genetic Variant NM_002479.6:c.363C>A (chr1-203085599-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_002479.6(MYOG):c.363C>A(p.Ile121Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.00767 in 1,614,218 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 51 hom. )

Consequence

MYOG
NM_002479.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.13

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-203085599-G-T is Benign according to our data. Variant chr1-203085599-G-T is described in ClinVar as Benign. ClinVar VariationId is 783015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 847 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.363C>A	p.Ile121Ile	synonymous	Exon 1 of 3	NP_002470.2
	MYOPARR	NR_160550.1		n.388-884G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOG	ENST00000241651.5	TSL:1 MANE Select	c.363C>A	p.Ile121Ile	synonymous	Exon 1 of 3	ENSP00000241651.4	P15173
MYOG	ENST00000944760.1		c.363C>A	p.Ile121Ile	synonymous	Exon 1 of 3	ENSP00000614819.1
MYOG	ENST00000944761.1		c.363C>A	p.Ile121Ile	synonymous	Exon 1 of 3	ENSP00000614820.1

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

848

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00824

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00825

Gnomad OTH

AF:

0.00955

GnomAD2 exomes

AF:

0.00639

AC:

1606

AN:

251420

AF XY:

0.00631

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00584

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.00916

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00789

AC:

11531

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00770

AC XY:

5598

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

33480

American (AMR)

AF:

0.00615

AC:

275

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0129

AC:

336

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00310

AC:

267

AN:

86258

European-Finnish (FIN)

AF:

0.00309

AC:

165

AN:

53416

Middle Eastern (MID)

AF:

0.00780

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00897

AC:

9973

AN:

1111994

Other (OTH)

AF:

0.00710

AC:

429

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

790

1580

2371

3161

3951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.00556

AC:

847

AN:

152354

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41588

American (AMR)

AF:

0.00823

AC:

126

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00823

AC:

560

AN:

68030

Other (OTH)

AF:

0.00945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00676

Hom.:

Bravo

AF:

0.00600

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00916

EpiControl

AF:

0.0108

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

(source)

DANN

Benign

0.81

PhyloP100

4.1

PromoterAI

-0.034

Neutral

(source)

Mutation Taster

=99/1

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

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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