rs11814752

Variant names:

• chr10-60194492-G-A
• rs11814752
• NM_020987.5:c.1887+1653C>T

Variant summary

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

The NM_020987.5(ANK3):​c.1887+1653C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,234 control chromosomes in the GnomAD database, including 1,028 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 0.10 (1028 hom., cov: 33)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_020987.5	MANE Select	c.1887+1653C>T		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.1836+1653C>T		intron	N/A	NP_001191333.1
	ANK3	NM_001320874.2		c.1887+1653C>T		intron	N/A	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.1887+1653C>T		intron	N/A	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.1869+1653C>T		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.1836+1653C>T		intron	N/A	ENSP00000425236.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15737 AN: 152118 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.104 AC: 15763 AN: 152234 Hom.: 1028 Cov.: 33 AF XY: 0.101 AC XY: 7529 AN XY: 74448

African (AFR) AF: 0.170 AC: 7056 AN: 41520

American (AMR) AF: 0.0723 AC: 1106 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 270 AN: 3466

East Asian (EAS) AF: 0.0650 AC: 337 AN: 5182

South Asian (SAS) AF: 0.118 AC: 569 AN: 4828

European-Finnish (FIN) AF: 0.0519 AC: 550 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5548 AN: 68020

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.0899 Hom.: 448

Bravo AF: 0.106

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.25
PhyloP100		-1.0
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: rs11814752; hg19: chr10-61954250;