rs148549519
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_020987.5(ANK3):āc.11825A>Gā(p.Lys3942Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,614,112 control chromosomes in the GnomAD database, including 1 homozygotes. 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). Synonymous variant affecting the same amino acid position (i.e. K3942K) has been classified as Likely benign.
Frequency
Consequence
NM_020987.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK3 | NM_020987.5 | c.11825A>G | p.Lys3942Arg | missense_variant | 37/44 | ENST00000280772.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.11825A>G | p.Lys3942Arg | missense_variant | 37/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00116 AC: 177AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000839 AC: 211AN: 251354Hom.: 0 AF XY: 0.000854 AC XY: 116AN XY: 135838
GnomAD4 exome AF: 0.00148 AC: 2160AN: 1461828Hom.: 1 Cov.: 33 AF XY: 0.00143 AC XY: 1039AN XY: 727218
GnomAD4 genome ? AF: 0.00116 AC: 177AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ANK3: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2022 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 3942 of the ANK3 protein (p.Lys3942Arg). This variant is present in population databases (rs148549519, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 210142). 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 22, 2015 | - - |
Intellectual disability-hypotonia-spasticity-sleep disorder syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at