Variant 10-60042792-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.149

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
ANK3	NM_020987.5 linkuse as main transcript	c.13066-33T>A		intron_variant		ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7 linkuse as main transcript	c.13066-33T>A		intron_variant		1	NM_020987.5	ENSP00000280772		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

88942

AN:

147456

Hom.:

26272

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.577

AC XY:

419299

AN XY:

726648

show subpopulations

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.:

AF XY:

0.609

AC XY:

43827

AN XY:

71972

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over