ENST00000373827.6:c.97-141731C>T

Variant names:

• chr10-60421370-G-A
• rs10994338
• ENST00000373827.6:c.97-141731C>T

Variant summary

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

The ENST00000373827.6(ANK3):​c.97-141731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 151,914 control chromosomes in the GnomAD database, including 912 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 0.080 (912 hom., cov: 31)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 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.64-141731C>T		intron	N/A	NP_001191333.1
	ANK3	NM_001204403.2		c.97-141731C>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.97-141731C>T		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.64-141731C>T		intron	N/A	ENSP00000425236.1
	ANK3	ENST00000622427.4	TSL:2	n.64-141731C>T		intron	N/A	ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12090 AN: 151796 Hom.: 907 Cov.: 31

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0696

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

GnomAD4 genome AF: 0.0796 AC: 12099 AN: 151914 Hom.: 912 Cov.: 31 AF XY: 0.0894 AC XY: 6638 AN XY: 74228

African (AFR) AF: 0.0153 AC: 634 AN: 41466

American (AMR) AF: 0.197 AC: 3005 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 155 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1144 AN: 5164

South Asian (SAS) AF: 0.142 AC: 682 AN: 4810

European-Finnish (FIN) AF: 0.188 AC: 1985 AN: 10542

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0638 AC: 4332 AN: 67924

Other (OTH) AF: 0.0717 AC: 151 AN: 2106

Alfa AF: 0.0753 Hom.: 1290

Bravo AF: 0.0795

Asia WGS AF: 0.194 AC: 672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.28
PhyloP100		-0.60
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: rs10994338; hg19: chr10-62181128;