rs149682716
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_020987.5(ANK3):c.2889C>T(p.Tyr963=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,609,334 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )
Consequence
ANK3
NM_020987.5 synonymous
NM_020987.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.306
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 10-60114284-G-A is Benign according to our data. Variant chr10-60114284-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.306 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00274 (418/152336) while in subpopulation AFR AF= 0.00964 (401/41576). AF 95% confidence interval is 0.00887. There are 2 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK3 | NM_020987.5 | c.2889C>T | p.Tyr963= | synonymous_variant | 26/44 | ENST00000280772.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK3 | ENST00000280772.7 | c.2889C>T | p.Tyr963= | synonymous_variant | 26/44 | 1 | NM_020987.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00275 AC: 418AN: 152218Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000777 AC: 192AN: 247068Hom.: 0 AF XY: 0.000516 AC XY: 69AN XY: 133644
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GnomAD4 exome AF: 0.000305 AC: 444AN: 1456998Hom.: 1 Cov.: 28 AF XY: 0.000270 AC XY: 196AN XY: 724874
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GnomAD4 genome ? AF: 0.00274 AC: 418AN: 152336Hom.: 2 Cov.: 32 AF XY: 0.00258 AC XY: 192AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | ANK3: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 24, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at