1-203085599-G-C

Variant names:

• chr1-203085599-G-C
• rs138462164
• NM_002479.6:c.363C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002479.6(MYOG):​c.363C>G​(p.Ile121Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I121I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYOG NM_002479.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

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>G	p.Ile121Met	missense	Exon 1 of 3	NP_002470.2
	MYOPARR	NR_160550.1		n.388-884G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOG	ENST00000241651.5	TSL:1 MANE Select	c.363C>G	p.Ile121Met	missense	Exon 1 of 3	ENSP00000241651.4	P15173
	MYOG	ENST00000944760.1		c.363C>G	p.Ile121Met	missense	Exon 1 of 3	ENSP00000614819.1
	MYOG	ENST00000944761.1		c.363C>G	p.Ile121Met	missense	Exon 1 of 3	ENSP00000614820.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.70	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.86		Gain of disorder (P = 0.0602)
MVP		0.97
MPC		1.2
ClinPred		1.0	D
GERP RS		4.7
PromoterAI		-0.042	Neutral
Varity_R		0.71
gMVP		0.68
Mutation Taster		=25/75	disease causing

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

Other links and lift over

dbSNP: rs138462164; hg19: chr1-203054727;