Variant 11-113387997-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178510.2(ANKK1):c.113A>T(p.Gln38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,570,750 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.113857836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKK1	NM_178510.2 linkuse as main transcript	c.113A>T	p.Gln38Leu	missense_variant	1/8	ENST00000303941.4
ANKK1	XM_011542736.3 linkuse as main transcript	c.113A>T	p.Gln38Leu	missense_variant	1/9
ANKK1	XM_017017475.2 linkuse as main transcript	c.113A>T	p.Gln38Leu	missense_variant	1/9
ANKK1	XM_011542737.3 linkuse as main transcript	c.113A>T	p.Gln38Leu	missense_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKK1	ENST00000303941.4 linkuse as main transcript	c.113A>T	p.Gln38Leu	missense_variant	1/8	1	NM_178510.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000281

AC:

AN:

178006

Hom.:

AF XY:

0.000325

AC XY:

AN XY:

98560

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.0000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000713

Gnomad NFE exome

AF:

0.000498

Gnomad OTH exome

AF:

0.000419

GnomAD4 exome

AF:

0.000706

AC:

1002

AN:

1418448

Hom.:

Cov.:

AF XY:

0.000670

AC XY:

471

AN XY:

702544

show subpopulations

Gnomad4 AFR exome

AF:

0.0000921

Gnomad4 AMR exome

AF:

0.000194

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.000821

Gnomad4 OTH exome

AF:

0.000848

GnomAD4 genome

AF:

0.000414

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000922

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000664

AC:

ExAC

AF:

0.000239

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.113A>T (p.Q38L) alteration is located in exon 1 (coding exon 1) of the ANKK1 gene. This alteration results from a A to T substitution at nucleotide position 113, causing the glutamine (Q) at amino acid position 38 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.59

MutationTaster

Benign

0.75

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.16

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.020

Polyphen

0.80

Vest4

0.25

MVP

0.59

MPC

0.26

ClinPred

0.059

GERP RS

3.3

Varity_R

0.32

gMVP

0.55

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