11-113396099-G-C

Variant names:

• chr11-113396099-G-C
• rs7118900
• NM_178510.2:c.715G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_178510.2(ANKK1):​c.715G>C​(p.Ala239Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 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. A239T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKK1 NM_178510.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 62 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKK1	NM_178510.2	c.715G>C	p.Ala239Pro	missense_variant	Exon 5 of 8	ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4	c.715G>C	p.Ala239Pro	missense_variant	Exon 5 of 8	1	NM_178510.2	ENSP00000306678.3
ANKK1	ENST00000542948.1	n.*269G>C		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000445810.1
ANKK1	ENST00000542948.1	n.*269G>C		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000445810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.0036	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Benign	0.73
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.71
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.3	L
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.42
Sift	Benign	0.10	T
Sift4G	Uncertain	0.053	T
Polyphen		0.72	P
Vest4		0.48
MutPred		0.79		Loss of MoRF binding (P = 0.0546);
MVP		0.74
MPC		0.35
ClinPred		0.57	D
GERP RS		2.5
Varity_R		0.32
gMVP		0.76
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs7118900; hg19: chr11-113266821;