Variant chr10-60042595-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.*19+77T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,367,112 control chromosomes in the GnomAD database, including 389,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40129 hom., cov: 32)

Exomes 𝑓: 0.76 ( 349668 hom. )

Consequence

ANK3
NM_020987.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.12

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 10-60042595-A-T is Benign according to our data. Variant chr10-60042595-A-T is described in ClinVar as [Benign]. Clinvar id is 1192392.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	UniProt
ANK3	NM_020987.5 linkuse as main transcript	c.*19+77T>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7 linkuse as main transcript	c.*19+77T>A		intron_variant		1	NM_020987.5		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109948

AN:

151970

Hom.:

40119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.731

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.819

Gnomad SAS

AF:

0.723

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.742

GnomAD4 exome

AF:

0.757

AC:

919278

AN:

1215024

Hom.:

349668

AF XY:

0.756

AC XY:

459760

AN XY:

608464

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.788

Gnomad4 EAS exome

AF:

0.783

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.687

Gnomad4 NFE exome

AF:

0.772

Gnomad4 OTH exome

AF:

0.750

GnomAD4 genome

AF:

0.723

AC:

110001

AN:

152088

Hom.:

40129

Cov.:

AF XY:

0.722

AC XY:

53704

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.652

Gnomad4 AMR

AF:

0.677

Gnomad4 ASJ

AF:

0.787

Gnomad4 EAS

AF:

0.819

Gnomad4 SAS

AF:

0.723

Gnomad4 FIN

AF:

0.684

Gnomad4 NFE

AF:

0.772

Gnomad4 OTH

AF:

0.743

Alfa

AF:

0.658

Hom.:

1957

Bravo

AF:

0.718

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.30

DANN

Benign

0.53

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