Genetic Variant MYOG:p.Ile121Ile (chr1-203085599-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 783015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 847 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOG	NM_002479.6 link	c.363C>A	p.Ile121Ile	synonymous_variant	Exon 1 of 3	ENST00000241651.5	NP_002470.2	P15173
MYOPARR	NR_160550.1 link	n.388-884G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOG	ENST00000241651.5 link	c.363C>A	p.Ile121Ile	synonymous_variant	Exon 1 of 3	1	NM_002479.6	ENSP00000241651.4		P15173

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

GnomAD3 exomes

AF:

0.00639

AC:

1606

AN:

251420

Hom.:

AF XY:

0.00631

AC XY:

858

AN XY:

135896

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 SAS exome

AF:

0.00304

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

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00615

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.00309

Gnomad4 NFE exome

AF:

0.00897

Gnomad4 OTH exome

AF:

0.00710

GnomAD4 genome

AF:

0.00556

AC:

847

AN:

152354

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00823

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00823

Gnomad4 OTH

AF:

0.00945

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.6

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over