4-71022459-C-T

Variant names:

• chr4-71022459-C-T
• rs11544786
• NM_000788.3:c.300C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000788.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	NM_000788.3	MANE Select	c.300C>T	p.Ala100Ala	synonymous	Exon 3 of 7	NP_000779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	ENST00000286648.10	TSL:1 MANE Select	c.300C>T	p.Ala100Ala	synonymous	Exon 3 of 7	ENSP00000286648.5
	DCK	ENST00000504952.1	TSL:3	c.300C>T	p.Ala100Ala	synonymous	Exon 3 of 8	ENSP00000421508.1
	DCK	ENST00000961150.1		c.300C>T	p.Ala100Ala	synonymous	Exon 3 of 8	ENSP00000631209.1

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

GnomAD2 exomes AF: 0.0493 AC: 12210 AN: 247858 AF XY: 0.0515

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 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

African (AFR) AF: 0.0104 AC: 347 AN: 33354

American (AMR) AF: 0.0379 AC: 1668 AN: 44050

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 3260 AN: 25960

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39578

South Asian (SAS) AF: 0.0573 AC: 4883 AN: 85250

European-Finnish (FIN) AF: 0.0405 AC: 2158 AN: 53290

Middle Eastern (MID) AF: 0.101 AC: 581 AN: 5736

European-Non Finnish (NFE) AF: 0.0623 AC: 69165 AN: 1109826

Other (OTH) AF: 0.0607 AC: 3658 AN: 60214

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

African (AFR) AF: 0.0100 AC: 416 AN: 41538

American (AMR) AF: 0.0456 AC: 697 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0579 AC: 279 AN: 4822

European-Finnish (FIN) AF: 0.0368 AC: 389 AN: 10582

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0623 AC: 4240 AN: 68010

Other (OTH) AF: 0.0626 AC: 132 AN: 2110

Alfa AF: 0.0579 Hom.: 227

Bravo AF: 0.0416

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.2
DANN	Benign	0.65
PhyloP100		0.55
Mutation Taster		=86/14	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: rs11544786; hg19: chr4-71888176;