9-110695537-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005592.4(MUSK):c.486+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,542,740 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005592.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUSK | ENST00000374448.9 | c.486+7G>C | splice_region_variant, intron_variant | Intron 4 of 14 | 5 | NM_005592.4 | ENSP00000363571.4 | |||
MUSK | ENST00000416899.7 | c.486+7G>C | splice_region_variant, intron_variant | Intron 4 of 13 | 5 | ENSP00000393608.3 | ||||
MUSK | ENST00000189978.10 | c.486+7G>C | splice_region_variant, intron_variant | Intron 4 of 13 | 5 | ENSP00000189978.6 | ||||
MUSK | ENST00000374439.1 | c.180+7G>C | splice_region_variant, intron_variant | Intron 2 of 3 | 5 | ENSP00000363562.2 |
Frequencies
GnomAD3 genomes AF: 0.00117 AC: 178AN: 152032Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000256 AC: 41AN: 160302Hom.: 0 AF XY: 0.000166 AC XY: 14AN XY: 84482
GnomAD4 exome AF: 0.000134 AC: 186AN: 1390590Hom.: 2 Cov.: 28 AF XY: 0.000119 AC XY: 82AN XY: 686534
GnomAD4 genome AF: 0.00117 AC: 178AN: 152150Hom.: 1 Cov.: 32 AF XY: 0.00101 AC XY: 75AN XY: 74394
ClinVar
Submissions by phenotype
not specified Benign:2
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MUSK-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 Benign:1
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Congenital myasthenic syndrome 9 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at