rs141536854
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001130987.2(DYSF):c.3337C>A(p.Arg1113Ser) 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 1,461,754 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. R1113C) has been classified as Likely benign.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3337C>A | p.Arg1113Ser | missense_variant | 30/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3283C>A | p.Arg1095Ser | missense_variant | 30/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3337C>A | p.Arg1113Ser | missense_variant | 30/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3283C>A | p.Arg1095Ser | missense_variant | 30/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251190Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135770
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461754Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727162
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 31, 2021 | This sequence change replaces arginine with serine at codon 1095 of the DYSF protein (p.Arg1095Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DYSF-related conditions. 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"). 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