chr10-60069508-ATTG-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_020987.5(ANK3):βc.11370_11372delβ(p.Asn3791del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000033 ( 0 hom., cov: 32)
Exomes π: 0.000034 ( 0 hom. )
Consequence
ANK3
NM_020987.5 inframe_deletion
NM_020987.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.02
Genes affected
ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_020987.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK3 | NM_020987.5 | c.11370_11372del | p.Asn3791del | inframe_deletion | 37/44 | ENST00000280772.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.11370_11372del | p.Asn3791del | inframe_deletion | 37/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152050Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250284Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135226
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461432Hom.: 0 AF XY: 0.0000303 AC XY: 22AN XY: 727004
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74378
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 14, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2022 | This variant is present in population databases (rs768074492, gnomAD 0.02%). This variant, c.11370_11372del, results in the deletion of 1 amino acid(s) of the ANK3 protein (p.Asn3791del), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with ANK3-related conditions. 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. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at