rs10821659

Variant names:

• chr10-60033666-A-G
• rs10821659
• NM_020987.5:c.*20-3840T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020987.5(ANK3):​c.*20-3840T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,944 control chromosomes in the GnomAD database, including 23,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23586 hom., cov: 31)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 publications found

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]

ANK3 Gene-Disease associations (from GenCC):

• intellectual disability-hypotonia-spasticity-sleep disorder syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• intellectual disability

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000232682 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.*20-3840T>C		intron_variant	Intron 43 of 43	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.*20-3840T>C		intron_variant	Intron 43 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83290 AN: 151826 Hom.: 23576 Cov.: 31

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.565

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.548 AC: 83340 AN: 151944 Hom.: 23586 Cov.: 31 AF XY: 0.539 AC XY: 39982 AN XY: 74242

African (AFR) AF: 0.505 AC: 20937 AN: 41426

American (AMR) AF: 0.455 AC: 6939 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2191 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5188

South Asian (SAS) AF: 0.442 AC: 2122 AN: 4802

European-Finnish (FIN) AF: 0.506 AC: 5311 AN: 10502

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42708 AN: 67978

Other (OTH) AF: 0.567 AC: 1197 AN: 2112

Alfa AF: 0.594 Hom.: 122801

Bravo AF: 0.540

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10821659; hg19: chr10-61793424;