16-10532912-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001424.6(EMP2):c.497G>A(p.Arg166His) variant causes a missense change. The variant allele was found at a frequency of 0.0000352 in 1,535,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001424.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151992Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000272 AC: 6AN: 220806Hom.: 0 AF XY: 0.0000167 AC XY: 2AN XY: 119928
GnomAD4 exome AF: 0.0000318 AC: 44AN: 1383398Hom.: 0 Cov.: 31 AF XY: 0.0000323 AC XY: 22AN XY: 681404
GnomAD4 genome AF: 0.0000658 AC: 10AN: 151992Hom.: 0 Cov.: 30 AF XY: 0.000108 AC XY: 8AN XY: 74220
ClinVar
Submissions by phenotype
not provided Uncertain:2
This variant is present in population databases (rs138530114, ExAC 0.02%). This sequence change replaces arginine with histidine at codon 166 of the EMP2 protein (p.Arg166His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant has not been reported in the literature in individuals affected with EMP2-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 disruptive. 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. -
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -
not specified Uncertain:1
Does not currently meet published gene-disease clinical validity criteria Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Nephrotic syndrome, type 10 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at