Genetic Variant MYOG:p.Asp18Gly (chr1-203085909-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002479.6(MYOG):c.53A>G(p.Asp18Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MYOG
NM_002479.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.64

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOG	NM_002479.6 link	c.53A>G	p.Asp18Gly	missense_variant	Exon 1 of 3	ENST00000241651.5	NP_002470.2	P15173
MYOPARR	NR_160550.1 link	n.388-574T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOG	ENST00000241651.5 link	c.53A>G	p.Asp18Gly	missense_variant	Exon 1 of 3	1	NM_002479.6	ENSP00000241651.4		P15173

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246310

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456942

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Jun 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.53A>G (p.D18G) alteration is located in exon 1 (coding exon 1) of the MYOG gene. This alteration results from a A to G substitution at nucleotide position 53, causing the aspartic acid (D) at amino acid position 18 to be replaced by a glycine (G). 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

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

-0.22

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.51

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.024

Polyphen

0.0010

Vest4

0.59

MutPred

0.87

Gain of catalytic residue at Y17 (P = 0.1128);

MVP

0.54

MPC

0.90

ClinPred

0.64

GERP RS

5.7

Varity_R

0.28

gMVP

0.58

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