Variant rs2393605 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+56T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 1,497,080 control chromosomes in the GnomAD database, including 427,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39829 hom., cov: 32)

Exomes 𝑓: 0.76 ( 387546 hom. )

Consequence

ANK3
NM_020987.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-60042616-A-T is Benign according to our data. Variant chr10-60042616-A-T is described in ClinVar as [Benign]. Clinvar id is 1192393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5 link	c.*19+56T>A		intron_variant	Intron 43 of 43	ENST00000280772.7	NP_066267.2	Q12955-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7 link	c.*19+56T>A		intron_variant	Intron 43 of 43	1	NM_020987.5	ENSP00000280772.1		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.722

AC:

109376

AN:

151508

Hom.:

39818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.732

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.680

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.740

GnomAD4 exome

AF:

0.757

AC:

1018700

AN:

1345454

Hom.:

387546

AF XY:

0.756

AC XY:

507009

AN XY:

670440

show subpopulations

Gnomad4 AFR exome

AF:

0.652

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.787

Gnomad4 EAS exome

AF:

0.784

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.686

Gnomad4 NFE exome

AF:

0.773

Gnomad4 OTH exome

AF:

0.751

GnomAD4 genome

AF:

0.722

AC:

109429

AN:

151626

Hom.:

39829

Cov.:

AF XY:

0.721

AC XY:

53383

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.677

Gnomad4 ASJ

AF:

0.787

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.680

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.742

Alfa

AF:

0.734

Hom.:

5039

Bravo

AF:

0.717

Asia WGS

AF:

0.756

AC:

2630

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

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.077

DANN

Benign

0.38

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