rs374780994
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001127178.3(PIGG):c.847G>A(p.Glu283Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,612,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
PIGG
NM_001127178.3 missense
NM_001127178.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.17
Genes affected
PIGG (HGNC:25985): (phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group)) This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31018114).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGG | NM_001127178.3 | c.847G>A | p.Glu283Lys | missense_variant | 5/13 | ENST00000453061.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGG | ENST00000453061.7 | c.847G>A | p.Glu283Lys | missense_variant | 5/13 | 1 | NM_001127178.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251474Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135914
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GnomAD4 exome AF: 0.0000507 AC: 74AN: 1460668Hom.: 0 Cov.: 29 AF XY: 0.0000468 AC XY: 34AN XY: 726730
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability, autosomal recessive 53 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 283 of the PIGG protein (p.Glu283Lys). This variant is present in population databases (rs374780994, gnomAD 0.005%). 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: 572292). 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
P;P;.;P;D;P
Vest4
MVP
MPC
0.37
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at