rs1322997651
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_024301.5(FKRP):c.1019A>T(p.Tyr340Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000169 in 1,542,924 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Y340Y) has been classified as Likely benign.
Frequency
Consequence
NM_024301.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.1019A>T | p.Tyr340Phe | missense_variant | 4/4 | ENST00000318584.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKRP | ENST00000318584.10 | c.1019A>T | p.Tyr340Phe | missense_variant | 4/4 | 1 | NM_024301.5 | P1 | |
FKRP | ENST00000391909.7 | c.1019A>T | p.Tyr340Phe | missense_variant | 4/4 | 2 | P1 | ||
FKRP | ENST00000597339.5 | n.247-5364A>T | intron_variant, non_coding_transcript_variant | 5 | |||||
FKRP | ENST00000600646.5 | n.247+7804A>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000663 AC: 1AN: 150840Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000180 AC: 25AN: 1392084Hom.: 0 Cov.: 32 AF XY: 0.0000175 AC XY: 12AN XY: 686150
GnomAD4 genome ? AF: 0.00000663 AC: 1AN: 150840Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73540
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2I Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2I;C1847759:Muscular dystrophy-dystroglycanopathy type B5;C3150413:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2024 | The c.1019A>T (p.Y340F) alteration is located in exon 4 (coding exon 1) of the FKRP gene. This alteration results from a A to T substitution at nucleotide position 1019, causing the tyrosine (Y) at amino acid position 340 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Walker-Warburg congenital muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2021 | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 340 of the FKRP protein (p.Tyr340Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 459226). 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