rs1555738103
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024301.5(FKRP):c.142del(p.Arg48ValfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G46G) has been classified as Likely benign.
Frequency
Consequence
NM_024301.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.142del | p.Arg48ValfsTer20 | frameshift_variant | 4/4 | ENST00000318584.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKRP | ENST00000318584.10 | c.142del | p.Arg48ValfsTer20 | frameshift_variant | 4/4 | 1 | NM_024301.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1453736Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 2AN XY: 722758
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Walker-Warburg congenital muscular dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2022 | This variant has not been reported in the literature in individuals affected with FKRP-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ser385*) have been determined to be pathogenic (PMID: 11592034, 12666124, 12707425, 14742276). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 459229). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg48Valfs*20) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 448 amino acid(s) of the FKRP protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at