rs578430
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005592.4(MUSK):c.2485G>A(p.Val829Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,600,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005592.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUSK | ENST00000374448.9 | c.2485G>A | p.Val829Met | missense_variant | Exon 15 of 15 | 5 | NM_005592.4 | ENSP00000363571.4 | ||
MUSK | ENST00000416899.7 | c.2461G>A | p.Val821Met | missense_variant | Exon 14 of 14 | 5 | ENSP00000393608.3 | |||
MUSK | ENST00000189978.10 | c.2227G>A | p.Val743Met | missense_variant | Exon 14 of 14 | 5 | ENSP00000189978.6 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000209 AC: 5AN: 238816Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 129006
GnomAD4 exome AF: 0.0000290 AC: 42AN: 1448496Hom.: 0 Cov.: 32 AF XY: 0.0000334 AC XY: 24AN XY: 718892
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
not provided Uncertain:1
BP4 -
Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 829 of the MUSK protein (p.Val829Met). This variant is present in population databases (rs578430, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1021233). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MUSK protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at