rs766309374
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032634.4(PIGO):āc.1363A>Gā(p.Thr455Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. T455T) has been classified as Uncertain significance.
Frequency
Consequence
NM_032634.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGO | NM_032634.4 | c.1363A>G | p.Thr455Ala | missense_variant | 7/11 | ENST00000378617.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGO | ENST00000378617.4 | c.1363A>G | p.Thr455Ala | missense_variant | 7/11 | 1 | NM_032634.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250806Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135600
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727204
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2020 | 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 alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PIGO-related disease. This variant is present in population databases (rs766309374, ExAC 0.002%). This sequence change replaces threonine with alanine at codon 455 of the PIGO protein (p.Thr455Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at