rs761199326
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_032634.4(PIGO):c.3113T>G(p.Leu1038Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,086 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 (★). Synonymous variant affecting the same amino acid position (i.e. L1038L) has been classified as Benign.
Frequency
Consequence
NM_032634.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGO | NM_032634.4 | c.3113T>G | p.Leu1038Arg | missense_variant | 10/11 | ENST00000378617.4 | |
PIGO | NM_001201484.2 | c.1862T>G | p.Leu621Arg | missense_variant | 12/13 | ||
PIGO | NM_152850.4 | c.1862T>G | p.Leu621Arg | missense_variant | 11/12 | ||
PIGO | XM_005251619.4 | c.3113T>G | p.Leu1038Arg | missense_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGO | ENST00000378617.4 | c.3113T>G | p.Leu1038Arg | missense_variant | 10/11 | 1 | NM_032634.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251456Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 727244
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74340
ClinVar
Submissions by phenotype
Hyperphosphatasia with intellectual disability syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2020 | This sequence change replaces leucine with arginine at codon 1038 of the PIGO protein (p.Leu1038Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is present in population databases (rs761199326, ExAC 0.003%). This variant has not been reported in the literature in individuals with PIGO-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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