9-35095313-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_032634.4(PIGO):c.253C>A(p.Pro85Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000119 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_032634.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000127 AC: 32AN: 251418Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135904
GnomAD4 exome AF: 0.000102 AC: 149AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.000105 AC XY: 76AN XY: 727248
GnomAD4 genome AF: 0.000283 AC: 43AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.000390 AC XY: 29AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.253C>A (p.P85T) alteration is located in exon 2 (coding exon 1) of the PIGO gene. This alteration results from a C to A substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 85 of the PIGO protein (p.Pro85Thr). This variant is present in population databases (rs745754359, gnomAD 0.05%). 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: 473224). 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. -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24417746) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at