rs11544786

Positions:

• chr4-71022459-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000788.3(DCK):​c.300C>T​(p.Ala100Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,609,454 control chromosomes in the GnomAD database, including 3,092 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 0.044 (208 hom., cov: 32)
  • Exomes 𝑓: 0.059 (2884 hom.)
• Consequence: DCK NM_000788.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

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:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=0.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCK	NM_000788.3	c.300C>T	p.Ala100Ala	synonymous_variant	3/7	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.84C>T	p.Ala28Ala	synonymous_variant	3/7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.300C>T	p.Ala100Ala	synonymous_variant	3/7	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6661 AN: 152078 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0623

GnomAD3 exomes AF: 0.0493 AC: 12210 AN: 247858 Hom.: 395 AF XY: 0.0515 AC XY: 6902 AN XY: 133962

Gnomad AFR exome AF: 0.00903

Gnomad AMR exome AF: 0.0351

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0525

Gnomad FIN exome AF: 0.0382

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0664

GnomAD4 exome AF: 0.0588 AC: 85735 AN: 1457258 Hom.: 2884 Cov.: 30 AF XY: 0.0595 AC XY: 43131 AN XY: 724806

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.0379

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.0573

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0623

Gnomad4 OTH exome AF: 0.0607

GnomAD4 genome AF: 0.0438 AC: 6661 AN: 152196 Hom.: 208 Cov.: 32 AF XY: 0.0432 AC XY: 3215 AN XY: 74412

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0600 Hom.: 197

Bravo AF: 0.0416

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.2
DANN	Benign	0.65

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: rs11544786; hg19: chr4-71888176;