10-60074815-G-A

Position:

chr10-60074815-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020987.5(ANK3):c.6066C>T(p.Ala2022Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,613,714 control chromosomes in the GnomAD database, including 7,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 541 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7316 hom. )

Consequence

ANK3
NM_020987.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.840

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-60074815-G-A is Benign according to our data. Variant chr10-60074815-G-A is described in ClinVar as [Benign]. Clinvar id is 128373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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.6066C>T	p.Ala2022Ala	synonymous_variant	37/44	ENST00000280772.7	NP_066267.2	Q12955-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7 linkuse as main transcript	c.6066C>T	p.Ala2022Ala	synonymous_variant	37/44	1	NM_020987.5	ENSP00000280772.1		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10923

AN:

152054

Hom.:

541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.0727

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0778

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0767

GnomAD3 exomes

AF:

0.0720

AC:

18023

AN:

250472

Hom.:

911

AF XY:

0.0724

AC XY:

9796

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.0510

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.0820

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.0953

GnomAD4 exome

AF:

0.0942

AC:

137697

AN:

1461542

Hom.:

7316

Cov.:

AF XY:

0.0925

AC XY:

67215

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0152

Gnomad4 AMR exome

AF:

0.0544

Gnomad4 ASJ exome

AF:

0.0633

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.0855

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.0855

GnomAD4 genome

AF:

0.0717

AC:

10917

AN:

152172

Hom.:

541

Cov.:

AF XY:

0.0673

AC XY:

5002

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.0727

Gnomad4 ASJ

AF:

0.0573

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0778

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.0759

Alfa

AF:

0.0961

Hom.:

1084

Bravo

AF:

0.0687

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

ANK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

DANN

Benign

0.66

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