rs4643786

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-71029543-C-A
• chr4-71029543-C-G
• chr4-71029543-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000788.3(DCK):​c.*165C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000237 in 422,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: DCK NM_000788.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.*165C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.*165C>A		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>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000237 AC: 1 AN: 422264 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 225994

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10064

American (AMR) AF: 0.00 AC: 0 AN: 14104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13924

East Asian (EAS) AF: 0.0000364 AC: 1 AN: 27460

South Asian (SAS) AF: 0.00 AC: 0 AN: 36886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1886

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 252362

Other (OTH) AF: 0.00 AC: 0 AN: 23608

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.24

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;