1-228165884-TGC-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001010867.4(IBA57):c.74_75delCG(p.Ala25GlyfsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000336 in 1,190,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001010867.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000336 AC: 4AN: 1190032Hom.: 0 AF XY: 0.00000173 AC XY: 1AN XY: 578294
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74 Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with IBA57-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala25Glyfs*52) in the IBA57 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IBA57 are known to be pathogenic (PMID: 23462291, 25971455, 27785568, 28671726). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at