NM_020987.5:c.115-45940A>G

Variant names:

• chr10-60325579-T-C
• rs10761482
• NM_020987.5:c.115-45940A>G

Variant summary

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

The NM_020987.5(ANK3):​c.115-45940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,992 control chromosomes in the GnomAD database, including 38,780 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 0.71 (38780 hom., cov: 31)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 37 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.115-45940A>G		intron_variant	Intron 1 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.64-45940A>G		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.115-45940A>G		intron_variant	Intron 1 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.97-45940A>G		intron_variant	Intron 2 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.115-45940A>G		intron_variant	Intron 1 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107675 AN: 151874 Hom.: 38765 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.709 AC: 107730 AN: 151992 Hom.: 38780 Cov.: 31 AF XY: 0.712 AC XY: 52865 AN XY: 74290

African (AFR) AF: 0.574 AC: 23789 AN: 41428

American (AMR) AF: 0.741 AC: 11322 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3705 AN: 5146

South Asian (SAS) AF: 0.904 AC: 4343 AN: 4804

European-Finnish (FIN) AF: 0.704 AC: 7443 AN: 10572

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51990 AN: 67976

Other (OTH) AF: 0.739 AC: 1558 AN: 2108

Alfa AF: 0.748 Hom.: 145001

Bravo AF: 0.699

Asia WGS AF: 0.777 AC: 2699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.0050
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: rs10761482; hg19: chr10-62085337;