NM_000788.3:c.208-3879T>G

Variant names:

• chr4-71018488-T-G
• rs4308342
• NM_000788.3:c.208-3879T>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.208-3879T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 150,074 control chromosomes in the GnomAD database, including 53,670 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 0.81 (53670 hom., cov: 27)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.208-3879T>G		intron_variant	Intron 2 of 6	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.-9-3879T>G		intron_variant	Intron 2 of 6		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.208-3879T>G		intron_variant	Intron 2 of 6	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.811 AC: 121601 AN: 149968 Hom.: 53664 Cov.: 27

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.971

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.810 AC: 121624 AN: 150074 Hom.: 53670 Cov.: 27 AF XY: 0.814 AC XY: 59752 AN XY: 73370

African (AFR) AF: 0.416 AC: 16829 AN: 40474

American (AMR) AF: 0.917 AC: 13815 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3327 AN: 3460

East Asian (EAS) AF: 0.952 AC: 4883 AN: 5130

South Asian (SAS) AF: 0.952 AC: 4500 AN: 4728

European-Finnish (FIN) AF: 0.971 AC: 10033 AN: 10332

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65354 AN: 67604

Other (OTH) AF: 0.852 AC: 1765 AN: 2072

Alfa AF: 0.941 Hom.: 51814

Bravo AF: 0.786

Asia WGS AF: 0.905 AC: 3138 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.45
PhyloP100		-0.65
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: rs4308342; hg19: chr4-71884205;