rs1002442

Positions:

• chr10-60043304-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.13066-545A>C		intron_variant		ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.13066-545A>C		intron_variant		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

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.175

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

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0681

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.149

Alfa AF: 0.190 Hom.: 3958

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1002442; hg19: chr10-61803062;