Variant chr11-113387894-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178510.2(ANKK1):c.10G>T(p.Asp4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,548,380 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.428

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047269166).

BP6

Variant 11-113387894-G-T is Benign according to our data. Variant chr11-113387894-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044435.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKK1	NM_178510.2 linkuse as main transcript	c.10G>T	p.Asp4Tyr	missense_variant	1/8	ENST00000303941.4
ANKK1	XM_011542736.3 linkuse as main transcript	c.10G>T	p.Asp4Tyr	missense_variant	1/9
ANKK1	XM_017017475.2 linkuse as main transcript	c.10G>T	p.Asp4Tyr	missense_variant	1/9
ANKK1	XM_011542737.3 linkuse as main transcript	c.10G>T	p.Asp4Tyr	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKK1	ENST00000303941.4 linkuse as main transcript	c.10G>T	p.Asp4Tyr	missense_variant	1/8	1	NM_178510.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00186

AC:

309

AN:

166134

Hom.:

AF XY:

0.00197

AC XY:

180

AN XY:

91520

show subpopulations

Gnomad AFR exome

AF:

0.000349

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00505

Gnomad FIN exome

AF:

0.000489

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00176

GnomAD4 exome

AF:

0.00226

AC:

3156

AN:

1396046

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1669

AN XY:

687890

show subpopulations

Gnomad4 AFR exome

AF:

0.000219

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00570

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00230

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152334

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00162

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000291

AC:

ESP6500EA

AF:

0.00212

AC:

ExAC

AF:

0.00127

AC:

145

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANKK1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2022

This variant is classified as likely 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

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.9

DANN

Benign

0.93

DEOGEN2

Benign

0.013

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.40

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.30

Sift

Benign

0.041

Sift4G

Benign

0.076

Polyphen

0.84

Vest4

0.22

MVP

0.67

MPC

0.075

ClinPred

0.0050

GERP RS

-1.3

Varity_R

0.072

gMVP

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