rs376931030
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_020987.5(ANK3):c.7940T>A(p.Val2647Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,613,894 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2647L) has been classified as Uncertain significance.
Frequency
Consequence
NM_020987.5 missense
Scores
Clinical Significance
Conservation
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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.7940T>A | p.Val2647Asp | missense_variant | 37/44 | ENST00000280772.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.7940T>A | p.Val2647Asp | missense_variant | 37/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000255 AC: 64AN: 250764Hom.: 0 AF XY: 0.000340 AC XY: 46AN XY: 135484
GnomAD4 exome AF: 0.000124 AC: 181AN: 1461832Hom.: 2 Cov.: 36 AF XY: 0.000175 AC XY: 127AN XY: 727212
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74258
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 04, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2022 | ClinVar contains an entry for this variant (Variation ID: 434162). This variant has not been reported in the literature in individuals affected with ANK3-related conditions. This variant is present in population databases (rs376931030, gnomAD 0.2%). This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2647 of the ANK3 protein (p.Val2647Asp). 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: "Benign"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at