rs770883682
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_001130987.2(DYSF):c.3161C>G(p.Thr1054Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,782 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. T1054I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3161C>G | p.Thr1054Arg | missense_variant | 29/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3107C>G | p.Thr1036Arg | missense_variant | 29/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3161C>G | p.Thr1054Arg | missense_variant | 29/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3107C>G | p.Thr1036Arg | missense_variant | 29/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250788Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135664
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727210
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces threonine with arginine at codon 1036 of the DYSF protein (p.Thr1036Arg). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected 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