rs150000731
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_004278.4(PIGL):c.4G>A(p.Glu2Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,750 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 (★★).
Frequency
Consequence
NM_004278.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251146Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135756
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727098
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
not provided Uncertain:2
ClinVar contains an entry for this variant (Variation ID: 159711). This variant has not been reported in the literature in individuals affected with PIGL-related conditions. 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. 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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2 of the PIGL protein (p.Glu2Lys). This variant is present in population databases (rs150000731, gnomAD 0.03%). -
BP4, PM2 -
CHIME syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at