rs866481043

Variant names:

• chr11-113388021-C-A
• rs866481043
• NM_178510.2:c.137C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113388021-C-A
• chr11-113388021-C-G
• chr11-113388021-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178510.2(ANKK1):​c.137C>A​(p.Thr46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,400,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T46M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKK1 NM_178510.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24806568).

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.137C>A	p.Thr46Lys	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.137C>A	p.Thr46Lys	missense	Exon 1 of 8	ENSP00000306678.3	Q8NFD2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400950 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690772

African (AFR) AF: 0.00 AC: 0 AN: 32060

American (AMR) AF: 0.00 AC: 0 AN: 40372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25260

East Asian (EAS) AF: 0.00 AC: 0 AN: 36742

South Asian (SAS) AF: 0.00 AC: 0 AN: 80386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1083724

Other (OTH) AF: 0.00 AC: 0 AN: 58094

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.18	N
PhyloP100		0.87
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.042	D
Sift4G	Uncertain	0.030	D
Polyphen		0.96	P
Vest4		0.17
MutPred		0.53		Gain of methylation at T46 (P = 0.022)
MVP		0.70
MPC		0.35
ClinPred		0.78	D
GERP RS		2.4
PromoterAI		0.12	Neutral
Varity_R		0.23
gMVP		0.42
Mutation Taster		=87/13	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: rs866481043; hg19: chr11-113258743;