NM_002479.6:c.148C>T

Variant names:

• chr1-203085814-G-A
• rs61739758
• NM_002479.6:c.148C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002479.6(MYOG):​c.148C>T​(p.Leu50Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYOG NM_002479.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3775481).

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.148C>T	p.Leu50Phe	missense	Exon 1 of 3	NP_002470.2
	MYOPARR	NR_160550.1		n.388-669G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOG	ENST00000241651.5	TSL:1 MANE Select	c.148C>T	p.Leu50Phe	missense	Exon 1 of 3	ENSP00000241651.4	P15173
	MYOG	ENST00000944760.1		c.148C>T	p.Leu50Phe	missense	Exon 1 of 3	ENSP00000614819.1
	MYOG	ENST00000944761.1		c.148C>T	p.Leu50Phe	missense	Exon 1 of 3	ENSP00000614820.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250332 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.84e-7 AC: 1 AN: 1461660 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.6	L
PhyloP100		2.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.31
Sift	Benign	0.27	T
Sift4G	Benign	0.27	T
Polyphen		0.98	D
Vest4		0.24
MutPred		0.34		Gain of methylation at K53 (P = 0.084)
MVP		0.71
MPC		1.3
ClinPred		0.56	D
GERP RS		5.7
PromoterAI		0.00060	Neutral
Varity_R		0.074
gMVP		0.26
Mutation Taster		=84/16	polymorphism

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: rs61739758; hg19: chr1-203054942;