11-113387907-T-G

Variant names:

• chr11-113387907-T-G
• rs1051656289
• NM_178510.2:c.23T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178510.2(ANKK1):​c.23T>G​(p.Leu8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,558,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (1 hom.)
• Consequence: ANKK1 NM_178510.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.264
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032028735).

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.23T>G	p.Leu8Arg	missense	Exon 1 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.23T>G	p.Leu8Arg	missense	Exon 1 of 8	ENSP00000306678.3	Q8NFD2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000220 AC: 31 AN: 1406520 Hom.: 1 Cov.: 31 AF XY: 0.0000173 AC XY: 12 AN XY: 694472

African (AFR) AF: 0.000402 AC: 13 AN: 32308

American (AMR) AF: 0.0000241 AC: 1 AN: 41420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 37014

South Asian (SAS) AF: 0.00 AC: 0 AN: 80596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088140

Other (OTH) AF: 0.000274 AC: 16 AN: 58364

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74498

African (AFR) AF: 0.0000481 AC: 2 AN: 41586

American (AMR) AF: 0.000196 AC: 3 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000756

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.1
DANN	Benign	0.56
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-0.26
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.069
Sift	Benign	0.96	T
Sift4G	Benign	0.86	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.42		Gain of solvent accessibility (P = 0.0018)
MVP		0.11
MPC		0.084
ClinPred		0.032	T
GERP RS		0.44
PromoterAI		-0.044	Neutral
Varity_R		0.063
gMVP		0.48
Mutation Taster		=99/1	polymorphism

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: rs1051656289; hg19: chr11-113258629;