4-71029543-C-T

Variant names:

• chr4-71029543-C-T
• rs4643786
• NM_000788.3:c.*165C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.*165C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.*165C>T		3_prime_UTR_variant	Exon 7 of 7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.*165C>T		3_prime_UTR_variant	Exon 7 of 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

African (AFR) AF: 0.413 AC: 4146 AN: 10038

American (AMR) AF: 0.930 AC: 13103 AN: 14094

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 13485 AN: 13920

East Asian (EAS) AF: 0.948 AC: 26009 AN: 27450

South Asian (SAS) AF: 0.961 AC: 35415 AN: 36870

European-Finnish (FIN) AF: 0.972 AC: 40784 AN: 41966

Middle Eastern (MID) AF: 0.927 AC: 1748 AN: 1886

European-Non Finnish (NFE) AF: 0.968 AC: 244124 AN: 252280

Other (OTH) AF: 0.923 AC: 21777 AN: 23582

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

African (AFR) AF: 0.410 AC: 16951 AN: 41314

American (AMR) AF: 0.917 AC: 14024 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3339 AN: 3472

East Asian (EAS) AF: 0.952 AC: 4935 AN: 5182

South Asian (SAS) AF: 0.953 AC: 4599 AN: 4828

European-Finnish (FIN) AF: 0.972 AC: 10182 AN: 10474

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

European-Non Finnish (NFE) AF: 0.967 AC: 65775 AN: 68006

Other (OTH) AF: 0.853 AC: 1800 AN: 2110

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
PhyloP100		-0.24
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: rs4643786; hg19: chr4-71895260;