10-60042584-C-A

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.*19+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,291,042 control chromosomes in the GnomAD database, including 365,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40090 hom., cov: 33)
  • Exomes 𝑓: 0.75 (325738 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.985

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=-0.88).
• BP6: Variant 10-60042584-C-A is Benign according to our data. Variant chr10-60042584-C-A is described in ClinVar as [Benign]. Clinvar id is 1192391.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.*19+88G>T		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.*19+88G>T		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109869 AN: 151930 Hom.: 40081 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.754 AC: 859332 AN: 1138994 Hom.: 325738 AF XY: 0.754 AC XY: 431270 AN XY: 572262

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.723 AC: 109920 AN: 152048 Hom.: 40090 Cov.: 33 AF XY: 0.722 AC XY: 53664 AN XY: 74298

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.742

Alfa AF: 0.764 Hom.: 77339

Bravo AF: 0.717

Asia WGS AF: 0.755 AC: 2626 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.27
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2393603; hg19: chr10-61802342;