Variant chr10-60042584-C-A 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.*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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.985

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=-0.88).

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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
ANK3	NM_020987.5 linkuse as main transcript	c.*19+88G>T		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.*19+88G>T		intron_variant		1	NM_020987.5	ENSP00000280772		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109869

AN:

151930

Hom.:

40081

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.722

AC XY:

53664

AN XY:

74298

show subpopulations

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: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

-0.88

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

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