rs769063859
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4
The NM_001010867.4(IBA57):āc.706C>Gā(p.Pro236Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,612,606 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 Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P236S) has been classified as Pathogenic.
Frequency
Consequence
NM_001010867.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IBA57 | NM_001010867.4 | c.706C>G | p.Pro236Ala | missense_variant | 3/3 | ENST00000366711.4 | |
IBA57 | NM_001310327.2 | c.127C>G | p.Pro43Ala | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IBA57 | ENST00000366711.4 | c.706C>G | p.Pro236Ala | missense_variant | 3/3 | 2 | NM_001010867.4 | P1 | |
IBA57 | ENST00000484749.5 | n.2706C>G | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
IBA57 | ENST00000546123.2 | n.426C>G | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249414Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135172
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460434Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 726514
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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 | Jul 19, 2022 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 236 of the IBA57 protein (p.Pro236Ala). This variant is present in population databases (rs769063859, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with IBA57-related conditions. ClinVar contains an entry for this variant (Variation ID: 521723). 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: "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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2022 | 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: 27785568) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at