rs148648652
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032634.4(PIGO):c.2891G>A(p.Cys964Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C964R) has been classified as Uncertain significance.
Frequency
Consequence
NM_032634.4 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 |
---|---|---|---|---|---|---|---|
PIGO | NM_032634.4 | c.2891G>A | p.Cys964Tyr | missense_variant | 9/11 | ENST00000378617.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGO | ENST00000378617.4 | c.2891G>A | p.Cys964Tyr | missense_variant | 9/11 | 1 | NM_032634.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250866Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135704
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727224
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces cysteine with tyrosine at codon 964 of the PIGO protein (p.Cys964Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs148648652, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with PIGO-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: "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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at