Genetic Variant ANKK1:p.Ser85Ser (chr11-113393550-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_178510.2(ANKK1):c.255T>C(p.Ser85Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,613,656 control chromosomes in the GnomAD database, including 340,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26532 hom., cov: 32)

Exomes 𝑓: 0.65 ( 314332 hom. )

Consequence

ANKK1
NM_178510.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

39 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=0.127 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKK1	NM_178510.2 link	c.255T>C	p.Ser85Ser	synonymous_variant	Exon 2 of 8	ENST00000303941.4	NP_848605.1	Q8NFD2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4 link	c.255T>C	p.Ser85Ser	synonymous_variant	Exon 2 of 8	1	NM_178510.2	ENSP00000306678.3		Q8NFD2
ANKK1	ENST00000542948.1 link	n.-85T>C		upstream_gene_variant		3		ENSP00000445810.1		H0YH32

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88048

AN:

151914

Hom.:

26528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.631

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.607

GnomAD2 exomes

AF:

0.608

AC:

151292

AN:

249024

AF XY:

0.616

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.677

Gnomad EAS exome

AF:

0.565

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.670

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.653

AC:

954259

AN:

1461624

Hom.:

314332

Cov.:

AF XY:

0.652

AC XY:

474157

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.407

AC:

13618

AN:

33478

American (AMR)

AF:

0.482

AC:

21566

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

17841

AN:

26136

East Asian (EAS)

AF:

0.583

AC:

23123

AN:

39694

South Asian (SAS)

AF:

0.589

AC:

50790

AN:

86246

European-Finnish (FIN)

AF:

0.682

AC:

36429

AN:

53400

Middle Eastern (MID)

AF:

0.620

AC:

3574

AN:

5768

European-Non Finnish (NFE)

AF:

0.673

AC:

748332

AN:

1111814

Other (OTH)

AF:

0.646

AC:

38986

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19544

39088

58633

78177

97721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.579

AC:

88087

AN:

152032

Hom.:

26532

Cov.:

AF XY:

0.578

AC XY:

42968

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.416

AC:

17242

AN:

41448

American (AMR)

AF:

0.541

AC:

8261

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2316

AN:

3470

East Asian (EAS)

AF:

0.565

AC:

2914

AN:

5158

South Asian (SAS)

AF:

0.569

AC:

2736

AN:

4812

European-Finnish (FIN)

AF:

0.667

AC:

7053

AN:

10570

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.668

AC:

45397

AN:

67986

Other (OTH)

AF:

0.604

AC:

1274

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1803

3607

5410

7214

9017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.634

Hom.:

93731

Bravo

AF:

0.562

Asia WGS

AF:

0.527

AC:

1830

AN:

3478

EpiCase

AF:

0.671

EpiControl

AF:

0.675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.8

(source)

DANN

Benign

0.40

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr11-113393550-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over