chr11-17719801-C-A

Variant names:

• chr11-17719801-C-A
• NM_002478.5:c.19C>A

Variant summary

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

The NM_002478.5(MYOD1):​c.19C>A​(p.Pro7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYOD1 NM_002478.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39407942).

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.19C>A	p.Pro7Thr	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.19C>A	p.Pro7Thr	missense	Exon 1 of 3	ENSP00000250003.3	P15172

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.15
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.39	T
MetaSVM	Pathogenic	1.2	D
MutationAssessor	Benign	1.2	L
PhyloP100		0.65
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.37		Gain of phosphorylation at P7 (P = 0.0346)
MVP		0.97
MPC		1.5
ClinPred		0.84	D
GERP RS		5.2
PromoterAI		-0.029	Neutral
Varity_R		0.24
gMVP		0.33
Mutation Taster		=85/15	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

hg19: chr11-17741348; COSMIC: COSV100000354;