chr4-521700-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001127178.3(PIGG):āc.1373G>Cā(p.Arg458Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 152,024 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R458C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127178.3 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 |
---|---|---|---|---|---|---|---|
PIGG | NM_001127178.3 | c.1373G>C | p.Arg458Pro | missense_variant | 8/13 | ENST00000453061.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGG | ENST00000453061.7 | c.1373G>C | p.Arg458Pro | missense_variant | 8/13 | 1 | NM_001127178.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152024Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74252
ClinVar
Submissions by phenotype
Intellectual disability, autosomal recessive 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2017 | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PIGG-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 458 of the PIGG protein (p.Arg458Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at