1-228165910-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001010867.4(IBA57):c.94G>A(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. A32D) has been classified as Uncertain significance.
Frequency
Consequence
NM_001010867.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152016Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000117 AC: 9AN: 76702Hom.: 0 AF XY: 0.0000680 AC XY: 3AN XY: 44130
GnomAD4 exome AF: 0.00000918 AC: 12AN: 1307044Hom.: 0 Cov.: 30 AF XY: 0.00000466 AC XY: 3AN XY: 643242
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152016Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74258
ClinVar
Submissions by phenotype
Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74 Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with IBA57-related conditions. This variant is present in population databases (rs780697842, gnomAD 0.06%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 32 of the IBA57 protein (p.Ala32Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at