NM_000788.3:c.207+9846A>G

Variant names:

• chr4-71008028-A-G
• rs12648166
• NM_000788.3:c.207+9846A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000788.3(DCK):​c.207+9846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,162 control chromosomes in the GnomAD database, including 20,519 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 0.48 (20519 hom., cov: 33)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 7 publications found

Genes affected

DCK (HGNC:2704): (deoxycytidine kinase) Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased deoxycytidine kinase activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity. [provided by RefSeq, Jul 2008]

MOB1B (HGNC:29801): (MOB kinase activator 1B) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000788.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	NM_000788.3	MANE Select	c.207+9846A>G		intron	N/A	NP_000779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	ENST00000286648.10	TSL:1 MANE Select	c.207+9846A>G		intron	N/A	ENSP00000286648.5
	DCK	ENST00000504952.1	TSL:3	c.207+9846A>G		intron	N/A	ENSP00000421508.1
	DCK	ENST00000504730.5	TSL:3	c.207+9846A>G		intron	N/A	ENSP00000425578.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72636 AN: 152044 Hom.: 20523 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72636 AN: 152162 Hom.: 20519 Cov.: 33 AF XY: 0.476 AC XY: 35426 AN XY: 74402

African (AFR) AF: 0.149 AC: 6199 AN: 41522

American (AMR) AF: 0.633 AC: 9676 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2506 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3113 AN: 5168

South Asian (SAS) AF: 0.531 AC: 2562 AN: 4826

European-Finnish (FIN) AF: 0.509 AC: 5388 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41496 AN: 67988

Other (OTH) AF: 0.551 AC: 1164 AN: 2114

Alfa AF: 0.554 Hom.: 49172

Bravo AF: 0.474

Asia WGS AF: 0.524 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs12648166; hg19: chr4-71873745;