rs140561049
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032634.4(PIGO):c.2186C>T(p.Pro729Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P729T) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGO | NM_032634.4 | c.2186C>T | p.Pro729Leu | missense_variant | 7/11 | ENST00000378617.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGO | ENST00000378617.4 | c.2186C>T | p.Pro729Leu | missense_variant | 7/11 | 1 | NM_032634.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460224Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726494
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 729 of the PIGO protein (p.Pro729Leu). This variant is present in population databases (rs140561049, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. ClinVar contains an entry for this variant (Variation ID: 473222). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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