11-113399652-C-T

Variant names:

• chr11-113399652-C-T
• rs2734848
• NM_178510.2:c.1683C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178510.2(ANKK1):​c.1683C>T​(p.Tyr561Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,601,578 control chromosomes in the GnomAD database, including 533,360 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 0.76 (44912 hom., cov: 34)
  • Exomes 𝑓: 0.82 (488448 hom.)
• Consequence: ANKK1 NM_178510.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 36 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=0.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178510.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKK1	NM_178510.2	MANE Select	c.1683C>T	p.Tyr561Tyr	synonymous	Exon 8 of 8	NP_848605.1	Q8NFD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKK1	ENST00000303941.4	TSL:1 MANE Select	c.1683C>T	p.Tyr561Tyr	synonymous	Exon 8 of 8	ENSP00000306678.3	Q8NFD2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115537 AN: 152056 Hom.: 44889 Cov.: 34

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.781

GnomAD2 exomes AF: 0.822 AC: 189081 AN: 229980 AF XY: 0.821

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.885

Gnomad ASJ exome AF: 0.770

Gnomad EAS exome AF: 0.961

Gnomad FIN exome AF: 0.855

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.818

GnomAD4 exome AF: 0.819 AC: 1187717 AN: 1449404 Hom.: 488448 Cov.: 96 AF XY: 0.819 AC XY: 589779 AN XY: 719928

African (AFR) AF: 0.571 AC: 18973 AN: 33252

American (AMR) AF: 0.878 AC: 37932 AN: 43196

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 20125 AN: 25872

East Asian (EAS) AF: 0.965 AC: 37639 AN: 39006

South Asian (SAS) AF: 0.818 AC: 68831 AN: 84144

European-Finnish (FIN) AF: 0.858 AC: 44676 AN: 52084

Middle Eastern (MID) AF: 0.743 AC: 4272 AN: 5748

European-Non Finnish (NFE) AF: 0.820 AC: 906600 AN: 1106186

Other (OTH) AF: 0.812 AC: 48669 AN: 59916

GnomAD4 genome AF: 0.760 AC: 115608 AN: 152174 Hom.: 44912 Cov.: 34 AF XY: 0.764 AC XY: 56883 AN XY: 74418

African (AFR) AF: 0.587 AC: 24348 AN: 41494

American (AMR) AF: 0.823 AC: 12589 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2693 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4947 AN: 5148

South Asian (SAS) AF: 0.811 AC: 3914 AN: 4826

European-Finnish (FIN) AF: 0.859 AC: 9120 AN: 10618

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55336 AN: 67994

Other (OTH) AF: 0.779 AC: 1646 AN: 2112

Alfa AF: 0.787 Hom.: 84751

Bravo AF: 0.754

Asia WGS AF: 0.829 AC: 2881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.26
DANN	Benign	0.29
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2734848; hg19: chr11-113270374; COSMIC: COSV58273447; COSMIC: COSV58273447;