NM_006790.3:c.17G>A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3PP5BS2
The NM_006790.3(MYOT):c.17G>A(p.Arg6His) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,613,856 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006790.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYOT | NM_006790.3 | c.17G>A | p.Arg6His | missense_variant | Exon 2 of 10 | ENST00000239926.9 | NP_006781.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOT | ENST00000239926.9 | c.17G>A | p.Arg6His | missense_variant | Exon 2 of 10 | 1 | NM_006790.3 | ENSP00000239926.4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250430Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135442
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727198
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74282
ClinVar
Submissions by phenotype
Myofibrillar myopathy 3 Pathogenic:1Uncertain:2
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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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 30407). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 21336781). This variant is present in population databases (rs387906882, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 6 of the MYOT protein (p.Arg6His). -
not provided Pathogenic:1
Reported previously in an individual with late-onset progressive limb-girdle muscle weakness and respiratory insufficiency (PMID: 21336781); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24928145, 20301582, 34426522, 21336781, 22349301) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at