rs771001595
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001127178.3(PIGG):c.2225G>A(p.Arg742Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000033 in 1,605,868 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R742W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001127178.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGG | NM_001127178.3 | c.2225G>A | p.Arg742Gln | missense_variant | 10/13 | ENST00000453061.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGG | ENST00000453061.7 | c.2225G>A | p.Arg742Gln | missense_variant | 10/13 | 1 | NM_001127178.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000575 AC: 14AN: 243452Hom.: 0 AF XY: 0.0000379 AC XY: 5AN XY: 131796
GnomAD4 exome AF: 0.0000282 AC: 41AN: 1453680Hom.: 0 Cov.: 32 AF XY: 0.0000291 AC XY: 21AN XY: 722352
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74346
ClinVar
Submissions by phenotype
Intellectual disability, autosomal recessive 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 05, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 742 of the PIGG protein (p.Arg742Gln). This variant is present in population databases (rs771001595, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PIGG-related conditions. ClinVar contains an entry for this variant (Variation ID: 476336). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at