4-71029543-C-T

Position:

• chr4-71029543-C-T

Variant summary

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

The NM_000788.3(DCK):​c.*165C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 573,968 control chromosomes in the GnomAD database, including 246,017 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 (54211 hom., cov: 32)
  • Exomes 𝑓: 0.95 (191806 hom.)
• Consequence: DCK NM_000788.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243

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=-0.83).
• 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	Protein	UniProt
DCK	NM_000788.3	c.*165C>T		3_prime_UTR_variant	7/7	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.*165C>T		3_prime_UTR_variant	7/7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.*165C>T		3_prime_UTR_variant	7/7	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122706 AN: 151764 Hom.: 54204 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.952

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

GnomAD4 exome AF: 0.949 AC: 400591 AN: 422086 Hom.: 191806 Cov.: 4 AF XY: 0.952 AC XY: 215000 AN XY: 225890

Gnomad4 AFR exome AF: 0.413

Gnomad4 AMR exome AF: 0.930

Gnomad4 ASJ exome AF: 0.969

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.961

Gnomad4 FIN exome AF: 0.972

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.923

GnomAD4 genome AF: 0.808 AC: 122731 AN: 151882 Hom.: 54211 Cov.: 32 AF XY: 0.813 AC XY: 60393 AN XY: 74304

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.853

Alfa AF: 0.878 Hom.: 7621

Bravo AF: 0.786

Asia WGS AF: 0.908 AC: 3145 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.60

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: rs4643786; hg19: chr4-71895260;