rs1251694138
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004204.5(PIGQ):c.689G>A(p.Arg230Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000213 in 1,407,398 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PIGQ
NM_004204.5 missense, splice_region
NM_004204.5 missense, splice_region
Scores
2
6
11
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
PIGQ (HGNC:14135): (phosphatidylinositol glycan anchor biosynthesis class Q) This gene is involved in the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIGQ | NM_004204.5 | c.689G>A | p.Arg230Gln | missense_variant, splice_region_variant | 2/11 | ENST00000321878.10 | NP_004195.2 | |
PIGQ | NM_148920.4 | c.689G>A | p.Arg230Gln | missense_variant, splice_region_variant | 2/10 | NP_683721.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGQ | ENST00000321878.10 | c.689G>A | p.Arg230Gln | missense_variant, splice_region_variant | 2/11 | 1 | NM_004204.5 | ENSP00000326674.6 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD3 exomes AF: 0.0000152 AC: 3AN: 197560Hom.: 0 AF XY: 0.00000921 AC XY: 1AN XY: 108582
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GnomAD4 exome AF: 0.00000213 AC: 3AN: 1407398Hom.: 0 Cov.: 33 AF XY: 0.00000288 AC XY: 2AN XY: 695626
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GnomAD4 genome Cov.: 34
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34
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 04, 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PIGQ-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 230 of the PIGQ protein (p.Arg230Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant also falls at the last nucleotide of exon 2 of the PIGQ coding sequence, which is part of the consensus splice site for this exon. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M;M
PrimateAI
Benign
T
PROVEAN
Benign
N;N;D;N;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;D;T;D
Polyphen
D;D;.;D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0933);Loss of MoRF binding (P = 0.0933);Loss of MoRF binding (P = 0.0933);Loss of MoRF binding (P = 0.0933);Loss of MoRF binding (P = 0.0933);
MVP
MPC
0.45
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at