10-60042803-G-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.13066-44C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 1,604,790 control chromosomes in the GnomAD database, including 461,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (40096 hom., cov: 32)
  • Exomes 𝑓: 0.76 (421091 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.699

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=-0.86).
• BP6: Variant 10-60042803-G-T is Benign according to our data. Variant chr10-60042803-G-T is described in ClinVar as [Benign]. Clinvar id is 1192428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.13066-44C>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.13066-44C>A		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.762 AC: 109868 AN: 144186 Hom.: 40085 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.777

GnomAD3 exomes AF: 0.726 AC: 180923 AN: 249058 Hom.: 66390 AF XY: 0.733 AC XY: 98657 AN XY: 134646

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.823

Gnomad SAS exome AF: 0.717

Gnomad FIN exome AF: 0.693

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.725

GnomAD4 exome AF: 0.758 AC: 1106365 AN: 1460506 Hom.: 421091 Cov.: 48 AF XY: 0.757 AC XY: 549935 AN XY: 726562

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.574

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.714

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.751

GnomAD4 genome AF: 0.762 AC: 109921 AN: 144284 Hom.: 40096 Cov.: 32 AF XY: 0.761 AC XY: 53667 AN XY: 70480

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.777

Alfa AF: 0.742 Hom.: 8839

Bravo AF: 0.717

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.3
Dann	Benign	0.72

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: rs2393607; hg19: chr10-61802561;