Variant 10-60042803-G-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.13066-44C>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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.699

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=-0.86).

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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
ANK3	NM_020987.5 linkuse as main transcript	c.13066-44C>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.13066-44C>A		intron_variant		1	NM_020987.5	ENSP00000280772		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

109868

AN:

144186

Hom.:

40085

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.757

AC XY:

549935

AN XY:

726562

show subpopulations

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.:

AF XY:

0.761

AC XY:

53667

AN XY:

70480

show subpopulations

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: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

-0.86

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

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