rs149439295
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032634.4(PIGO):c.3118G>T(p.Val1040Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,056 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. V1040I) has been classified as Likely benign.
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.3118G>T | p.Val1040Phe | missense_variant | 10/11 | ENST00000378617.4 | |
PIGO | NM_001201484.2 | c.1867G>T | p.Val623Phe | missense_variant | 12/13 | ||
PIGO | NM_152850.4 | c.1867G>T | p.Val623Phe | missense_variant | 11/12 | ||
PIGO | XM_005251619.4 | c.3118G>T | p.Val1040Phe | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGO | ENST00000378617.4 | c.3118G>T | p.Val1040Phe | missense_variant | 10/11 | 1 | NM_032634.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 01, 2022 | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1040 of the PIGO protein (p.Val1040Phe). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with PIGO-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at