rs200919668
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_020987.5(ANK3):āc.4585T>Cā(p.Ser1529Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000395 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1529C) has been classified as Likely benign.
Frequency
Consequence
NM_020987.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK3 | NM_020987.5 | c.4585T>C | p.Ser1529Pro | missense_variant | 37/44 | ENST00000280772.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.4585T>C | p.Ser1529Pro | missense_variant | 37/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251274Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135804
GnomAD4 exome AF: 0.000413 AC: 604AN: 1461796Hom.: 0 Cov.: 34 AF XY: 0.000400 AC XY: 291AN XY: 727210
GnomAD4 genome AF: 0.000223 AC: 34AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 09, 2014 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2022 | Unlikely to be causative of ANK3-related neurodevelopmental disorder (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1529 of the ANK3 protein (p.Ser1529Pro). This variant is present in population databases (rs200919668, gnomAD 0.03%). 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: 210162). 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) performed at Invitae indicates that this missense variant is not expected to disrupt ANK3 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