10-60043304-T-G

Variant names:

• chr10-60043304-T-G
• rs1002442
• NM_020987.5:c.13066-545A>C

Variant summary

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

The NM_020987.5(ANK3):​c.13066-545A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 985,230 control chromosomes in the GnomAD database, including 17,143 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 0.14 (1868 hom., cov: 32)
  • Exomes 𝑓: 0.19 (15275 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 7 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)

ENSG00000232682 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.13066-545A>C		intron_variant	Intron 42 of 43	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.13066-545A>C		intron_variant	Intron 42 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20964 AN: 152092 Hom.: 1869 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.189 AC: 157324 AN: 833020 Hom.: 15275 Cov.: 33 AF XY: 0.190 AC XY: 72926 AN XY: 384672

African (AFR) AF: 0.0326 AC: 515 AN: 15790

American (AMR) AF: 0.105 AC: 103 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 679 AN: 5154

East Asian (EAS) AF: 0.0625 AC: 227 AN: 3630

South Asian (SAS) AF: 0.139 AC: 2293 AN: 16456

European-Finnish (FIN) AF: 0.124 AC: 35 AN: 282

Middle Eastern (MID) AF: 0.208 AC: 337 AN: 1622

European-Non Finnish (NFE) AF: 0.195 AC: 148361 AN: 761802

Other (OTH) AF: 0.175 AC: 4774 AN: 27300

GnomAD4 genome AF: 0.138 AC: 20954 AN: 152210 Hom.: 1868 Cov.: 32 AF XY: 0.133 AC XY: 9871 AN XY: 74412

African (AFR) AF: 0.0428 AC: 1778 AN: 41566

American (AMR) AF: 0.117 AC: 1789 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 453 AN: 3470

East Asian (EAS) AF: 0.0681 AC: 353 AN: 5182

South Asian (SAS) AF: 0.127 AC: 611 AN: 4806

European-Finnish (FIN) AF: 0.140 AC: 1487 AN: 10606

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13932 AN: 67980

Other (OTH) AF: 0.149 AC: 315 AN: 2114

Alfa AF: 0.173 Hom.: 5469

Bravo AF: 0.131

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.65
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1002442; hg19: chr10-61803062;