rs753650660
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004204.5(PIGQ):āc.77A>Gā(p.Glu26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E26Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_004204.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIGQ | NM_004204.5 | c.77A>G | p.Glu26Gly | missense_variant | 2/11 | ENST00000321878.10 | |
PIGQ | NM_148920.4 | c.77A>G | p.Glu26Gly | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIGQ | ENST00000321878.10 | c.77A>G | p.Glu26Gly | missense_variant | 2/11 | 1 | NM_004204.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000323 AC: 8AN: 247826Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134582
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460094Hom.: 0 Cov.: 40 AF XY: 0.0000110 AC XY: 8AN XY: 726428
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74368
ClinVar
Submissions by phenotype
Epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 16, 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. 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 glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PIGQ-related disease. This variant is present in population databases (rs753650660, ExAC 0.02%). This sequence change replaces glutamic acid with glycine at codon 26 of the PIGQ protein (p.Glu26Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at