chr10-60166650-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_020987.5(ANK3):c.2555G>A(p.Arg852His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,510 control chromosomes in the GnomAD database, including 2 homozygotes. 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_020987.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK3 | NM_020987.5 | c.2555G>A | p.Arg852His | missense_variant | 23/44 | ENST00000280772.7 | |
ANK3 | NM_001204404.2 | c.2504G>A | p.Arg835His | missense_variant | 23/44 | ||
ANK3 | NM_001320874.2 | c.2555G>A | p.Arg852His | missense_variant | 23/43 | ||
ANK3 | NM_001204403.2 | c.2537G>A | p.Arg846His | missense_variant | 24/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.2555G>A | p.Arg852His | missense_variant | 23/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000239 AC: 60AN: 250860Hom.: 0 AF XY: 0.000229 AC XY: 31AN XY: 135600
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461250Hom.: 2 Cov.: 30 AF XY: 0.000171 AC XY: 124AN XY: 726934
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2016 | A variant of uncertain significance has been identified in the ANK3 gene. The R852H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R852H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the R852H variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces arginine with histidine at codon 852 of the ANK3 protein (p.Arg852His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs190358169, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ANK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 252732). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Oct 16, 2015 | - - |
Intellectual disability-hypotonia-spasticity-sleep disorder syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 17, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at