NM_002478.5:c.142C>T

Variant names:

• chr11-17719924-C-T
• rs761828232
• NM_002478.5:c.142C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002478.5(MYOD1):​c.142C>T​(p.Pro48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P48T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYOD1 NM_002478.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

MYOD1 (HGNC:7611): (myogenic differentiation 1) This gene encodes a nuclear protein that belongs to the basic helix-loop-helix family of transcription factors and the myogenic factors subfamily. It regulates muscle cell differentiation by inducing cell cycle arrest, a prerequisite for myogenic initiation. The protein is also involved in muscle regeneration. It activates its own transcription which may stabilize commitment to myogenesis. [provided by RefSeq, Jul 2008]

MYOD1 Gene-Disease associations (from GenCC):

• myopathy, congenital, with diaphragmatic defects, respiratory insufficiency, and dysmorphic facies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002478.5. 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
	MYOD1	NM_002478.5	MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 1 of 3	NP_002469.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOD1	ENST00000250003.4	TSL:1 MANE Select	c.142C>T	p.Pro48Ser	missense	Exon 1 of 3	ENSP00000250003.3	P15172

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.38
Sift	Benign	0.065	T
Sift4G	Benign	0.13	T
Polyphen		0.89	P
Vest4		0.27
MutPred		0.50		Gain of phosphorylation at P48 (P = 0.0563)
MVP		0.95
MPC		0.95
ClinPred		0.98	D
GERP RS		5.2
PromoterAI		-0.013	Neutral
Varity_R		0.46
gMVP		0.50
Mutation Taster		=80/20	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: rs761828232; hg19: chr11-17741471;