10-60614275-A-G

Variant names:

• chr10-60614275-A-G
• rs4143096
• ENST00000373827.6:c.96+911T>C

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+911T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,152 control chromosomes in the GnomAD database, including 2,137 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 0.15 (2137 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204403.2	c.96+911T>C		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+911T>C		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000510382.1	n.101+911T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22770 AN: 152034 Hom.: 2139 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.150 AC: 22757 AN: 152152 Hom.: 2137 Cov.: 32 AF XY: 0.155 AC XY: 11525 AN XY: 74356

African (AFR) AF: 0.0367 AC: 1526 AN: 41562

American (AMR) AF: 0.148 AC: 2256 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 864 AN: 3468

East Asian (EAS) AF: 0.103 AC: 536 AN: 5190

South Asian (SAS) AF: 0.270 AC: 1299 AN: 4804

European-Finnish (FIN) AF: 0.239 AC: 2518 AN: 10546

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13099 AN: 67982

Other (OTH) AF: 0.152 AC: 322 AN: 2116

Alfa AF: 0.164 Hom.: 272

Bravo AF: 0.135

Asia WGS AF: 0.164 AC: 566 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.76
PhyloP100		0.45
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: rs4143096; hg19: chr10-62374033;