4-70993963-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000788.3(DCK):​c.91+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,469,492 control chromosomes in the GnomAD database, including 253 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 0.014 ( 23 hom., cov: 32)
Exomes 𝑓: 0.017 ( 230 hom. )

Consequence

DCK
NM_000788.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

Publications

4 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0142 (2165/152340) while in subpopulation NFE AF = 0.0197 (1343/68022). AF 95% confidence interval is 0.0189. There are 23 homozygotes in GnomAd4. There are 1068 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCKNM_000788.3 linkc.91+37G>C intron_variant Intron 1 of 6 ENST00000286648.10 NP_000779.1 P27707F5CTF3
DCKXM_047449689.1 linkc.-180G>C 5_prime_UTR_variant Exon 1 of 7 XP_047305645.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCKENST00000286648.10 linkc.91+37G>C intron_variant Intron 1 of 6 1 NM_000788.3 ENSP00000286648.5 P27707

Frequencies

GnomAD3 genomes
AF:
0.0142
AC:
2165
AN:
152224
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00398
Gnomad AMI
AF:
0.0537
Gnomad AMR
AF:
0.0141
Gnomad ASJ
AF:
0.0233
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00785
Gnomad FIN
AF:
0.0205
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0197
Gnomad OTH
AF:
0.0186
GnomAD2 exomes
AF:
0.0147
AC:
3445
AN:
234998
AF XY:
0.0150
show subpopulations
Gnomad AFR exome
AF:
0.00369
Gnomad AMR exome
AF:
0.00939
Gnomad ASJ exome
AF:
0.0244
Gnomad EAS exome
AF:
0.0000574
Gnomad FIN exome
AF:
0.0214
Gnomad NFE exome
AF:
0.0200
Gnomad OTH exome
AF:
0.0184
GnomAD4 exome
AF:
0.0166
AC:
21845
AN:
1317152
Hom.:
230
Cov.:
19
AF XY:
0.0164
AC XY:
10859
AN XY:
662174
show subpopulations
African (AFR)
AF:
0.00340
AC:
104
AN:
30570
American (AMR)
AF:
0.0102
AC:
441
AN:
43368
Ashkenazi Jewish (ASJ)
AF:
0.0209
AC:
523
AN:
25052
East Asian (EAS)
AF:
0.0000773
AC:
3
AN:
38818
South Asian (SAS)
AF:
0.00727
AC:
599
AN:
82398
European-Finnish (FIN)
AF:
0.0209
AC:
1101
AN:
52604
Middle Eastern (MID)
AF:
0.0444
AC:
244
AN:
5492
European-Non Finnish (NFE)
AF:
0.0183
AC:
17949
AN:
983082
Other (OTH)
AF:
0.0158
AC:
881
AN:
55768
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1105
2210
3316
4421
5526
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
624
1248
1872
2496
3120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0142
AC:
2165
AN:
152340
Hom.:
23
Cov.:
32
AF XY:
0.0143
AC XY:
1068
AN XY:
74496
show subpopulations
African (AFR)
AF:
0.00397
AC:
165
AN:
41586
American (AMR)
AF:
0.0142
AC:
217
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.0233
AC:
81
AN:
3472
East Asian (EAS)
AF:
0.000386
AC:
2
AN:
5176
South Asian (SAS)
AF:
0.00766
AC:
37
AN:
4832
European-Finnish (FIN)
AF:
0.0205
AC:
218
AN:
10622
Middle Eastern (MID)
AF:
0.0476
AC:
14
AN:
294
European-Non Finnish (NFE)
AF:
0.0197
AC:
1343
AN:
68022
Other (OTH)
AF:
0.0184
AC:
39
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
106
213
319
426
532
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
28
56
84
112
140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0107
Hom.:
6
Bravo
AF:
0.0137
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
4.3
DANN
Benign
0.72
PhyloP100
0.39
PromoterAI
-0.050
Neutral
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9997790; hg19: chr4-71859680; API