rs747784107
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033453.4(ITPA):c.520G>A(p.Ala174Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. A174V) has been classified as Uncertain significance.
Frequency
Consequence
NM_033453.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPA | NM_033453.4 | c.520G>A | p.Ala174Thr | missense_variant | 8/8 | ENST00000380113.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPA | ENST00000380113.8 | c.520G>A | p.Ala174Thr | missense_variant | 8/8 | 1 | NM_033453.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250730Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135566
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461562Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 727072
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Inosine triphosphatase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces alanine with threonine at codon 174 of the ITPA protein (p.Ala174Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs747784107, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ITPA-related conditions. 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. 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