chr12-80707999-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002469.3(MYF6):c.280C>T(p.Arg94Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002469.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYF6 | NM_002469.3 | c.280C>T | p.Arg94Trp | missense_variant | 1/3 | ENST00000228641.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYF6 | ENST00000228641.4 | c.280C>T | p.Arg94Trp | missense_variant | 1/3 | 1 | NM_002469.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal dominant centronuclear myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | This variant has not been reported in the literature in individuals affected with MYF6-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1039100). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 94 of the MYF6 protein (p.Arg94Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at