ENST00000373827.6:c.96+96132C>T

Variant names:

• chr10-60519054-G-A
• rs2153522
• ENST00000373827.6:c.96+96132C>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+96132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,042 control chromosomes in the GnomAD database, including 3,607 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 0.21 (3607 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373827.6. 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_001204404.2		c.63+53411C>T		intron	N/A	NP_001191333.1
	ANK3	NM_001204403.2		c.96+96132C>T		intron	N/A	NP_001191332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000373827.6	TSL:1	c.96+96132C>T		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.63+53411C>T		intron	N/A	ENSP00000425236.1
	ANK3	ENST00000510382.1	TSL:2	n.102-10429C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31815 AN: 151924 Hom.: 3602 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.209 AC: 31844 AN: 152042 Hom.: 3607 Cov.: 32 AF XY: 0.219 AC XY: 16267 AN XY: 74300

African (AFR) AF: 0.184 AC: 7654 AN: 41506

American (AMR) AF: 0.276 AC: 4220 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1744 AN: 5134

South Asian (SAS) AF: 0.349 AC: 1680 AN: 4810

European-Finnish (FIN) AF: 0.275 AC: 2906 AN: 10578

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12398 AN: 67972

Other (OTH) AF: 0.192 AC: 404 AN: 2102

Alfa AF: 0.194 Hom.: 5175

Bravo AF: 0.210

Asia WGS AF: 0.347 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.36
PhyloP100		0.0040
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: rs2153522; hg19: chr10-62278812;