11-113393550-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178510.2(ANKK1):c.255T>C(p.Ser85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,613,656 control chromosomes in the GnomAD database, including 340,864 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 0.58 (26532 hom., cov: 32)
  • Exomes 𝑓: 0.65 (314332 hom.)
• Consequence: ANKK1 NM_178510.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=0.127 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKK1	NM_178510.2	c.255T>C	p.Ser85=	synonymous_variant	2/8	ENST00000303941.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKK1	ENST00000303941.4	c.255T>C	p.Ser85=	synonymous_variant	2/8	1	NM_178510.2	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88048 AN: 151914 Hom.: 26528 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.607

GnomAD3 exomes AF: 0.608 AC: 151292 AN: 249024 Hom.: 47064 AF XY: 0.616 AC XY: 83249 AN XY: 135114

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.565

Gnomad SAS exome AF: 0.581

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.653 AC: 954259 AN: 1461624 Hom.: 314332 Cov.: 67 AF XY: 0.652 AC XY: 474157 AN XY: 727090

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.589

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.579 AC: 88087 AN: 152032 Hom.: 26532 Cov.: 32 AF XY: 0.578 AC XY: 42968 AN XY: 74308

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.604

Alfa AF: 0.651 Hom.: 64212

Bravo AF: 0.562

Asia WGS AF: 0.527 AC: 1830 AN: 3478

EpiCase AF: 0.671

EpiControl AF: 0.675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	4.8
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs17115439; hg19: chr11-113264272; COSMIC: COSV58270926; COSMIC: COSV58270926;