11-76926631-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018367.7(ACER3):āc.178G>Cā(p.Glu60Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,604,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_018367.7 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: 0.0000263 AC: 4AN: 152058Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250794Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135558
GnomAD4 exome AF: 0.0000310 AC: 45AN: 1452934Hom.: 0 Cov.: 36 AF XY: 0.0000290 AC XY: 21AN XY: 723324
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152058Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74256
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 60 of the ACER3 protein (p.Glu60Gln). This variant is present in population databases (rs781035647, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ACER3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1975821). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACER3 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