rs745774108
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_024301.5(FKRP):c.1441C>G(p.Pro481Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P481H) has been classified as Uncertain significance.
Frequency
Consequence
NM_024301.5 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 |
---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.1441C>G | p.Pro481Ala | missense_variant | 4/4 | ENST00000318584.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKRP | ENST00000318584.10 | c.1441C>G | p.Pro481Ala | missense_variant | 4/4 | 1 | NM_024301.5 | P1 | |
FKRP | ENST00000391909.7 | c.1441C>G | p.Pro481Ala | missense_variant | 4/4 | 2 | P1 | ||
FKRP | ENST00000597339.5 | n.247-4942C>G | intron_variant, non_coding_transcript_variant | 5 | |||||
FKRP | ENST00000600646.5 | n.247+8226C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000106 AC: 26AN: 246072Hom.: 0 AF XY: 0.0000819 AC XY: 11AN XY: 134328
GnomAD4 exome AF: 0.0000500 AC: 73AN: 1460624Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38AN XY: 726568
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 02, 2023 | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27439679, 30564623) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 29, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 24, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2023 | The p.P481A variant (also known as c.1441C>G), located in coding exon 1 of the FKRP gene, results from a C to G substitution at nucleotide position 1441. The proline at codon 481 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Walker-Warburg congenital muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at