rs200272055
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004204.5(PIGQ):c.335G>A(p.Arg112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000677 in 1,610,580 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. R112P) has been classified as Uncertain significance.
Frequency
Consequence
NM_004204.5 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 |
---|---|---|---|---|---|---|---|
PIGQ | NM_004204.5 | c.335G>A | p.Arg112Gln | missense_variant | 2/11 | ENST00000321878.10 | |
PIGQ | NM_148920.4 | c.335G>A | p.Arg112Gln | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGQ | ENST00000321878.10 | c.335G>A | p.Arg112Gln | missense_variant | 2/11 | 1 | NM_004204.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152186Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000460 AC: 11AN: 239202Hom.: 0 AF XY: 0.0000459 AC XY: 6AN XY: 130646
GnomAD4 exome AF: 0.0000583 AC: 85AN: 1458276Hom.: 0 Cov.: 40 AF XY: 0.0000593 AC XY: 43AN XY: 725270
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152304Hom.: 0 Cov.: 34 AF XY: 0.000175 AC XY: 13AN XY: 74464
ClinVar
Submissions by phenotype
Epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 112 of the PIGQ protein (p.Arg112Gln). This variant is present in population databases (rs200272055, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with PIGQ-related conditions. ClinVar contains an entry for this variant (Variation ID: 526268). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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