9-128166246-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001131016.2(CIZ1):c.2648G>A(p.Arg883Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,469,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001131016.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CIZ1 | NM_001131016.2 | c.2648G>A | p.Arg883Gln | missense_variant | Exon 17 of 17 | ENST00000372938.10 | NP_001124488.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000561 AC: 8AN: 142616Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000323 AC: 5AN: 154990Hom.: 0 AF XY: 0.0000124 AC XY: 1AN XY: 80822
GnomAD4 exome AF: 0.0000151 AC: 20AN: 1326876Hom.: 0 Cov.: 33 AF XY: 0.0000108 AC XY: 7AN XY: 647866
GnomAD4 genome AF: 0.0000561 AC: 8AN: 142616Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 2AN XY: 69116
ClinVar
Submissions by phenotype
Dystonic disorder 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2171235). This variant has not been reported in the literature in individuals affected with CIZ1-related conditions. This variant is present in population databases (rs772580580, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 883 of the CIZ1 protein (p.Arg883Gln). -
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at