10-60042792-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020987.5(ANK3):c.13066-33T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,608,346 control chromosomes in the GnomAD database, including 272,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (26290 hom., cov: 32)
  • Exomes 𝑓: 0.58 (245943 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-60042792-A-T is Benign according to our data. Variant chr10-60042792-A-T is described in ClinVar as [Benign]. Clinvar id is 1192395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.13066-33T>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.13066-33T>A		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.603 AC: 88942 AN: 147456 Hom.: 26272 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.608

GnomAD3 exomes AF: 0.576 AC: 144076 AN: 250324 Hom.: 42225 AF XY: 0.577 AC XY: 78006 AN XY: 135252

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.474

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.762

Gnomad SAS exome AF: 0.570

Gnomad FIN exome AF: 0.545

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.578 AC: 844301 AN: 1460780 Hom.: 245943 Cov.: 47 AF XY: 0.577 AC XY: 419299 AN XY: 726648

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.603 AC: 89006 AN: 147566 Hom.: 26290 Cov.: 32 AF XY: 0.609 AC XY: 43827 AN XY: 71972

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.611

Alfa AF: 0.569 Hom.: 4568

Bravo AF: 0.587

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability-hypotonia-spasticity-sleep disorder syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.1
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9888033; hg19: chr10-61802550;