rs1185775471
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005592.4(MUSK):c.359-2dup variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,332,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005592.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUSK | NM_005592.4 | c.359-2dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000374448.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUSK | ENST00000374448.9 | c.359-2dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005592.4 | P4 | |||
MUSK | ENST00000189978.10 | c.359-2dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
MUSK | ENST00000374439.1 | c.53-2dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
MUSK | ENST00000416899.7 | c.359-2dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000138 AC: 2AN: 145398Hom.: 0 AF XY: 0.0000130 AC XY: 1AN XY: 77104
GnomAD4 exome AF: 0.00000225 AC: 3AN: 1332618Hom.: 0 Cov.: 26 AF XY: 0.00000304 AC XY: 2AN XY: 658834
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 05, 2016 | - - |
Fetal akinesia deformation sequence 1;C4225368:Congenital myasthenic syndrome 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | This sequence change falls in intron 3 of the MUSK gene. It does not directly change the encoded amino acid sequence of the MUSK protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD no frequency). 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: 435906). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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