Variant 11-113399293-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178510.2(ANKK1):c.1324G>C(p.Gly442Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,600,436 control chromosomes in the GnomAD database, including 359,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.60 ( 28188 hom., cov: 34)

Exomes 𝑓: 0.67 ( 330846 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.236

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1771816E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKK1	NM_178510.2 linkuse as main transcript	c.1324G>C	p.Gly442Arg	missense_variant	8/8	ENST00000303941.4	NP_848605.1	Q8NFD2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4 linkuse as main transcript	c.1324G>C	p.Gly442Arg	missense_variant	8/8	1	NM_178510.2	ENSP00000306678.3		Q8NFD2

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91200

AN:

152048

Hom.:

28182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.637

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.641

AC:

146108

AN:

227906

Hom.:

47348

AF XY:

0.644

AC XY:

79571

AN XY:

123482

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.628

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.637

Gnomad NFE exome

AF:

0.687

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.673

AC:

974510

AN:

1448270

Hom.:

330846

Cov.:

AF XY:

0.672

AC XY:

483406

AN XY:

719012

show subpopulations

Gnomad4 AFR exome

AF:

0.433

Gnomad4 AMR exome

AF:

0.666

Gnomad4 ASJ exome

AF:

0.632

Gnomad4 EAS exome

AF:

0.444

Gnomad4 SAS exome

AF:

0.641

Gnomad4 FIN exome

AF:

0.646

Gnomad4 NFE exome

AF:

0.695

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.600

AC:

91238

AN:

152166

Hom.:

28188

Cov.:

AF XY:

0.597

AC XY:

44390

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.447

Gnomad4 AMR

AF:

0.618

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.457

Gnomad4 SAS

AF:

0.625

Gnomad4 FIN

AF:

0.637

Gnomad4 NFE

AF:

0.687

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.660

Hom.:

18562

Bravo

AF:

0.598

TwinsUK

AF:

0.692

AC:

2565

ALSPAC

AF:

0.695

AC:

2679

ESP6500AA

AF:

0.485

AC:

2069

ESP6500EA

AF:

0.695

AC:

5896

ExAC

AF:

0.623

AC:

75059

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.024

DANN

Benign

0.40

DEOGEN2

Benign

0.0039

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.16

PrimateAI

Benign

0.19

PROVEAN

Benign

3.1

REVEL

Benign

0.023

Sift

Benign

0.51

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.032

MPC

0.070

ClinPred

0.00068

GERP RS

1.8

Varity_R

0.099

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over