4-70993635-C-T

Variant summary

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

The ENST00000509617.1(DCK):c.-104-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 480,874 control chromosomes in the GnomAD database, including 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 0.022 (111 hom., cov: 32)
  • Exomes 𝑓: 0.028 (408 hom.)
• Consequence: DCK ENST00000509617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCK	NM_000788.3			upstream_gene_variant		ENST00000286648.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCK	ENST00000286648.10			upstream_gene_variant		1	NM_000788.3	P1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3374 AN: 152068 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0280 AC: 9217 AN: 328692 Hom.: 408 Cov.: 2 AF XY: 0.0285 AC XY: 4916 AN XY: 172556

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.0368

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.0450

Gnomad4 FIN exome AF: 0.00422

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0292

GnomAD4 genome AF: 0.0221 AC: 3370 AN: 152182 Hom.: 111 Cov.: 32 AF XY: 0.0234 AC XY: 1738 AN XY: 74388

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0443

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.00272 Hom.: 0

Bravo AF: 0.0256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.063
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2306744; hg19: chr4-71859352;