rs936869

chr4-71026319-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000788.3(DCK):c.666-346T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,084 control chromosomes in the GnomAD database, including 54,255 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 (54255 hom., cov: 32)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	UniProt
DCK	NM_000788.3	c.666-346T>C		intron_variant		ENST00000286648.10
DCK	XM_047449689.1	c.450-346T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCK	ENST00000286648.10	c.666-346T>C		intron_variant		1	NM_000788.3	P1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122823 AN: 151966 Hom.: 54248 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.808 AC: 122848 AN: 152084 Hom.: 54255 Cov.: 32 AF XY: 0.812 AC XY: 60410 AN XY: 74356

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.854

Alfa AF: 0.850 Hom.: 7910

Bravo AF: 0.786

Asia WGS AF: 0.909 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.57

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: rs936869; hg19: chr4-71892036;