chr1-228166132-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_001010867.4(IBA57):c.316A>T(p.Thr106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,521,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T106A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001010867.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IBA57 | NM_001010867.4 | c.316A>T | p.Thr106Ser | missense_variant | 1/3 | ENST00000366711.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IBA57 | ENST00000366711.4 | c.316A>T | p.Thr106Ser | missense_variant | 1/3 | 2 | NM_001010867.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000162 AC: 2AN: 123468Hom.: 0 AF XY: 0.0000290 AC XY: 2AN XY: 68900
GnomAD4 exome AF: 0.00000365 AC: 5AN: 1369250Hom.: 0 Cov.: 33 AF XY: 0.00000444 AC XY: 3AN XY: 675702
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152072Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74282
ClinVar
Submissions by phenotype
Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 106 of the IBA57 protein (p.Thr106Ser). This variant is present in population databases (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with IBA57-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Thr106 amino acid residue in IBA57. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27785568, 28671726, 28803783, 32348839). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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