10-60519366-C-T

Variant names:

• chr10-60519366-C-T
• rs10994397
• ENST00000373827.6:c.96+95820G>A

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+95820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 152,092 control chromosomes in the GnomAD database, including 1,215 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 0.10 (1215 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 39 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 (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.63+53099G>A		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001204403.2	c.96+95820G>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.96+95820G>A		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.63+53099G>A		intron_variant	Intron 1 of 43	2		ENSP00000425236.1
ANK3	ENST00000510382.1	n.102-10741G>A		intron_variant	Intron 2 of 2	2
ANK3	ENST00000622427.4	n.63+53099G>A		intron_variant	Intron 1 of 32	2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15158 AN: 151974 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0873

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

GnomAD4 genome AF: 0.0997 AC: 15166 AN: 152092 Hom.: 1215 Cov.: 32 AF XY: 0.109 AC XY: 8125 AN XY: 74314

African (AFR) AF: 0.0662 AC: 2750 AN: 41522

American (AMR) AF: 0.206 AC: 3143 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0776 AC: 269 AN: 3466

East Asian (EAS) AF: 0.310 AC: 1595 AN: 5148

South Asian (SAS) AF: 0.160 AC: 768 AN: 4812

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10564

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0653 AC: 4442 AN: 68002

Other (OTH) AF: 0.0883 AC: 186 AN: 2106

Alfa AF: 0.0807 Hom.: 3826

Bravo AF: 0.102

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-0.62
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: rs10994397; hg19: chr10-62279124;