rs3808942

Variant names:

• chr10-60391090-C-T
• rs3808942
• ENST00000373827.6:c.97-111451G>A

Variant summary

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

The ENST00000373827.6(ANK3):​c.97-111451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,166 control chromosomes in the GnomAD database, including 41,728 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 0.74 (41728 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.64-111451G>A		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001204403.2	c.97-111451G>A		intron_variant	Intron 2 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.97-111451G>A		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.64-111451G>A		intron_variant	Intron 1 of 43	2		ENSP00000425236.1
ANK3	ENST00000622427.4	n.64-111451G>A		intron_variant	Intron 1 of 32	2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112193 AN: 152048 Hom.: 41703 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.738 AC: 112268 AN: 152166 Hom.: 41728 Cov.: 32 AF XY: 0.742 AC XY: 55213 AN XY: 74386

African (AFR) AF: 0.657 AC: 27261 AN: 41492

American (AMR) AF: 0.738 AC: 11278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2706 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3806 AN: 5172

South Asian (SAS) AF: 0.898 AC: 4336 AN: 4830

European-Finnish (FIN) AF: 0.732 AC: 7750 AN: 10592

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52664 AN: 68012

Other (OTH) AF: 0.740 AC: 1565 AN: 2114

Alfa AF: 0.762 Hom.: 168351

Bravo AF: 0.729

Asia WGS AF: 0.782 AC: 2717 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.77
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3808942; hg19: chr10-62150848;