11-17719801-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOD1	NM_002478.5	c.19C>A	p.Pro7Thr	missense_variant	Exon 1 of 3	ENST00000250003.4	NP_002469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOD1	ENST00000250003.4	c.19C>A	p.Pro7Thr	missense_variant	Exon 1 of 3	1	NM_002478.5	ENSP00000250003.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19C>A (p.P7T) alteration is located in exon 1 (coding exon 1) of the MYOD1 gene. This alteration results from a C to A substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a threonine (T). 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	0.15
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
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
Varity_R		0.24
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17741348; COSMIC: COSV100000354;