Variant 11-113399438-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_178510.2(ANKK1):c.1469A>G(p.His490Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,596,064 control chromosomes in the GnomAD database, including 177,903 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 12138 hom., cov: 33)

Exomes 𝑓: 0.47 ( 165765 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.500

Variant links:

Genes affected

ANKK1 (HGNC:21027): (ankyrin repeat and kinase domain containing 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways. This gene is closely linked to DRD2 gene (GeneID:1813) on chr 11, and a well studied restriction fragment length polymorphism (RFLP) designated TaqIA, was originally associated with the DRD2 gene, however, later was determined to be located in exon 8 of ANKK1 gene (PMIDs: 18621654, 15146457), where it causes a nonconservative amino acid substitution. It is not clear if this gene plays any role in neuropsychiatric disorders previously associated with Taq1A RFLP. [provided by RefSeq, Sep 2009]

ANKK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.7886806E-5).

BP6

Variant 11-113399438-A-G is Benign according to our data. Variant chr11-113399438-A-G is described in ClinVar as [Benign]. Clinvar id is 3060675.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKK1	NM_178510.2 linkuse as main transcript	c.1469A>G	p.His490Arg	missense_variant	8/8	ENST00000303941.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKK1	ENST00000303941.4 linkuse as main transcript	c.1469A>G	p.His490Arg	missense_variant	8/8	1	NM_178510.2	P1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55676

AN:

151902

Hom.:

12150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.0612

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.387

AC:

85778

AN:

221404

Hom.:

19003

AF XY:

0.400

AC XY:

47893

AN XY:

119796

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.0562

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.467

AC:

674674

AN:

1444042

Hom.:

165765

Cov.:

106

AF XY:

0.466

AC XY:

333989

AN XY:

716418

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.0595

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.463

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.366

AC:

55667

AN:

152022

Hom.:

12138

Cov.:

AF XY:

0.360

AC XY:

26779

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.0608

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.506

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.479

Hom.:

41465

Bravo

AF:

0.347

TwinsUK

AF:

0.509

AC:

1886

ALSPAC

AF:

0.518

AC:

1998

ESP6500AA

AF:

0.164

AC:

665

ESP6500EA

AF:

0.502

AC:

4205

ExAC

AF:

0.377

AC:

45379

Asia WGS

AF:

0.185

AC:

643

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANKK1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0070

DANN

Benign

0.18

DEOGEN2

Benign

0.0044

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.39

MetaRNN

Benign

0.000048

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

1.4

REVEL

Benign

0.088

Sift

Benign

0.77

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.012

MPC

0.071

ClinPred

0.026

GERP RS

-9.3

Varity_R

0.042

gMVP

0.097

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