chr12-80708000-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_002469.3(MYF6):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,866 control chromosomes in the GnomAD database, including 1 homozygotes. 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. R94W) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYF6 | NM_002469.3 | c.281G>A | p.Arg94Gln | missense_variant | 1/3 | ENST00000228641.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYF6 | ENST00000228641.4 | c.281G>A | p.Arg94Gln | missense_variant | 1/3 | 1 | NM_002469.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250736Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135782
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461866Hom.: 1 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727228
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Centronuclear Myopathy, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Autosomal dominant centronuclear myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 30, 2020 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MYF6-related conditions. ClinVar contains an entry for this variant (Variation ID: 310507). This variant is present in population databases (rs201273759, ExAC 0.01%). This sequence change replaces arginine with glutamine at codon 94 of the MYF6 protein (p.Arg94Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at