Genetic Variant MYOG:p.Tyr35Tyr (chr1-203085857-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002479.6(MYOG):c.105C>T(p.Tyr35Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,613,990 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 36 hom. )

Consequence

MYOG
NM_002479.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.56

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-203085857-G-A is Benign according to our data. Variant chr1-203085857-G-A is described in ClinVar as [Benign]. Clinvar id is 773418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.56 with no splicing effect.

BS2

High AC in GnomAd4 at 483 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOG	NM_002479.6 link	c.105C>T	p.Tyr35Tyr	synonymous_variant	Exon 1 of 3	ENST00000241651.5	NP_002470.2	P15173
MYOPARR	NR_160550.1 link	n.388-626G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOG	ENST00000241651.5 link	c.105C>T	p.Tyr35Tyr	synonymous_variant	Exon 1 of 3	1	NM_002479.6	ENSP00000241651.4		P15173

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

483

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00851

Gnomad SAS

AF:

0.0160

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00349

AC:

876

AN:

250798

Hom.:

AF XY:

0.00412

AC XY:

559

AN XY:

135570

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00653

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00248

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00407

AC:

5947

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

3101

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00564

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00375

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00317

AC:

483

AN:

152238

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00853

Gnomad4 SAS

AF:

0.0160

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00338

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00304

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00320

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

- -

May 16, 2018

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

-0.83

CADD

Benign

0.47

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