11-113388000-C-A

Variant names:

• chr11-113388000-C-A
• rs554233180
• NM_178510.2:c.116C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_178510.2(ANKK1):​c.116C>A​(p.Ala39Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,570,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A39V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ANKK1 NM_178510.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.808
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.33609122).

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.116C>A	p.Ala39Glu	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.116C>A	p.Ala39Glu	missense	Exon 1 of 8	ENSP00000306678.3	Q8NFD2

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000174 AC: 31 AN: 177654 AF XY: 0.000193

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000300

Gnomad ASJ exome AF: 0.000809

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000422

GnomAD4 exome AF: 0.000147 AC: 208 AN: 1418050 Hom.: 0 Cov.: 31 AF XY: 0.000151 AC XY: 106 AN XY: 702274

African (AFR) AF: 0.000368 AC: 12 AN: 32566

American (AMR) AF: 0.000436 AC: 18 AN: 41272

Ashkenazi Jewish (ASJ) AF: 0.00110 AC: 28 AN: 25456

East Asian (EAS) AF: 0.00 AC: 0 AN: 37554

South Asian (SAS) AF: 0.0000369 AC: 3 AN: 81290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39598

Middle Eastern (MID) AF: 0.000708 AC: 4 AN: 5650

European-Non Finnish (NFE) AF: 0.000110 AC: 120 AN: 1095746

Other (OTH) AF: 0.000390 AC: 23 AN: 58918

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152332 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74500

African (AFR) AF: 0.0000481 AC: 2 AN: 41566

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.000397

ExAC AF: 0.000145 AC: 17

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	0.045
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.81
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.53
MutPred		0.90		Gain of disorder (P = 0.0316)
MVP		0.46
MPC		0.34
ClinPred		0.092	T
GERP RS		-0.47
PromoterAI		0.084	Neutral
Varity_R		0.40
gMVP		0.75
Mutation Taster		=81/19	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: rs554233180; hg19: chr11-113258722;