rs773802422
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001127178.3(PIGG):āc.2392T>Cā(p.Tyr798His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001127178.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGG | NM_001127178.3 | c.2392T>C | p.Tyr798His | missense_variant | 11/13 | ENST00000453061.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGG | ENST00000453061.7 | c.2392T>C | p.Tyr798His | missense_variant | 11/13 | 1 | NM_001127178.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251488Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461424Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727038
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Intellectual disability, autosomal recessive 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2018 | This sequence change replaces tyrosine with histidine at codon 798 of the PIGG protein (p.Tyr798His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs773802422, ExAC 0.001%). This variant has not been reported in the literature in individuals with PIGG-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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