rs147211454
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000144.5(FXN):c.340_352del(p.Ala114ThrfsTer15) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
FXN
NM_000144.5 frameshift
NM_000144.5 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.11
Genes affected
FXN (HGNC:3951): (frataxin) This nuclear gene encodes a mitochondrial protein which belongs to the FRATAXIN family. The protein functions in regulating mitochondrial iron transport and respiration. The expansion of intronic trinucleotide repeat GAA from 8-33 repeats to >90 repeats results in Friedreich ataxia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FXN | NM_000144.5 | c.340_352del | p.Ala114ThrfsTer15 | frameshift_variant | 3/5 | ENST00000484259.3 | |
FXN | NM_181425.3 | c.340_352del | p.Ala114ThrfsTer15 | frameshift_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FXN | ENST00000484259.3 | c.340_352del | p.Ala114ThrfsTer15 | frameshift_variant | 3/5 | 3 | NM_000144.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
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31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461740Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727176
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GnomAD4 genome ? Cov.: 31
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ClinVar
Not reported inComputational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at