chr10-60562860-T-A

Variant names:

• chr10-60562860-T-A
• rs958852
• ENST00000373827.6:c.96+52326A>T

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+52326A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,628 control chromosomes in the GnomAD database, including 35,382 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 0.68 (35382 hom., cov: 33)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.63+9605A>T		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001204403.2	c.96+52326A>T		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.96+52326A>T		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.63+9605A>T		intron_variant	Intron 1 of 43	2		ENSP00000425236.1
ANK3	ENST00000510382.1	n.101+52326A>T		intron_variant	Intron 2 of 2	2
ANK3	ENST00000622427.4	n.63+9605A>T		intron_variant	Intron 1 of 32	2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102508 AN: 151510 Hom.: 35373 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.676 AC: 102562 AN: 151628 Hom.: 35382 Cov.: 33 AF XY: 0.685 AC XY: 50720 AN XY: 74064

African (AFR) AF: 0.523 AC: 21636 AN: 41330

American (AMR) AF: 0.724 AC: 11048 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2814 AN: 3464

East Asian (EAS) AF: 0.823 AC: 4234 AN: 5142

South Asian (SAS) AF: 0.881 AC: 4249 AN: 4822

European-Finnish (FIN) AF: 0.727 AC: 7618 AN: 10482

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48579 AN: 67808

Other (OTH) AF: 0.695 AC: 1467 AN: 2110

Alfa AF: 0.687 Hom.: 4507

Bravo AF: 0.668

Asia WGS AF: 0.814 AC: 2815 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		0.13
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: rs958852; hg19: chr10-62322618;