rs777363797
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_153747.2(PIGC):c.865A>C(p.Lys289Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000575 in 1,565,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_153747.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIGC | ENST00000344529.5 | c.865A>C | p.Lys289Gln | missense_variant | Exon 2 of 2 | 1 | NM_153747.2 | ENSP00000356701.3 | ||
C1orf105 | ENST00000367727.9 | c.22-3315T>G | intron_variant | Intron 1 of 6 | 1 | NM_139240.4 | ENSP00000356700.4 | |||
PIGC | ENST00000484368.1 | n.96+2230A>C | intron_variant | Intron 1 of 4 | 1 | |||||
PIGC | ENST00000367728.1 | c.865A>C | p.Lys289Gln | missense_variant | Exon 1 of 1 | 6 | ENSP00000356702.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000189 AC: 4AN: 211532Hom.: 0 AF XY: 0.0000265 AC XY: 3AN XY: 113216
GnomAD4 exome AF: 0.00000425 AC: 6AN: 1412954Hom.: 0 Cov.: 30 AF XY: 0.00000573 AC XY: 4AN XY: 698396
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.865A>C (p.K289Q) alteration is located in exon 2 (coding exon 1) of the PIGC gene. This alteration results from a A to C substitution at nucleotide position 865, causing the lysine (K) at amino acid position 289 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PIGC-related conditions. This variant is present in population databases (rs777363797, gnomAD 0.02%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 289 of the PIGC protein (p.Lys289Gln). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at