rs377584268
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_004204.5(PIGQ):c.1291G>A(p.Val431Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,612,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 1 hom. )
Consequence
PIGQ
NM_004204.5 missense
NM_004204.5 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 6.83
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 Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14799988).
BP6
?
Variant 16-579136-G-A is Benign according to our data. Variant chr16-579136-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 456030.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGQ | NM_004204.5 | c.1291G>A | p.Val431Ile | missense_variant | 7/11 | ENST00000321878.10 | |
PIGQ | NM_148920.4 | c.1291G>A | p.Val431Ile | missense_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGQ | ENST00000321878.10 | c.1291G>A | p.Val431Ile | missense_variant | 7/11 | 1 | NM_004204.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152174Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000224 AC: 56AN: 250358Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135692
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GnomAD4 exome AF: 0.000173 AC: 252AN: 1460704Hom.: 1 Cov.: 31 AF XY: 0.000173 AC XY: 126AN XY: 726670
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152292Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11AN XY: 74446
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 26, 2024 | The c.1291G>A (p.V431I) alteration is located in exon 7 (coding exon 6) of the PIGQ gene. This alteration results from a G to A substitution at nucleotide position 1291, causing the valine (V) at amino acid position 431 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2022 | - - |
Epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;D
Polyphen
B;B;D;.
Vest4
MVP
MPC
0.16
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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