chr15-48340956-C-T

Position:

• chr15-48340956-C-T

Variant summary

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

The NM_001025248.2(DUT):​c.557-333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,112 control chromosomes in the GnomAD database, including 28,323 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 0.54 (28323 hom., cov: 32)
• Consequence: DUT NM_001025248.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892

Genes affected

DUT (HGNC:3078): (deoxyuridine triphosphatase) This gene encodes an essential enzyme of nucleotide metabolism. The encoded protein forms a ubiquitous, homotetrameric enzyme that hydrolyzes dUTP to dUMP and pyrophosphate. This reaction serves two cellular purposes: providing a precursor (dUMP) for the synthesis of thymine nucleotides needed for DNA replication, and limiting intracellular pools of dUTP. Elevated levels of dUTP lead to increased incorporation of uracil into DNA, which induces extensive excision repair mediated by uracil glycosylase. This repair process, resulting in the removal and reincorporation of dUTP, is self-defeating and leads to DNA fragmentation and cell death. Alternative splicing of this gene leads to different isoforms that localize to either the mitochondrion or nucleus. A related pseudogene is located on chromosome 19. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUT	NM_001025248.2	c.557-333C>T		intron_variant		ENST00000331200.8	NP_001020419.1
DUT	NM_001330286.2	c.302-333C>T		intron_variant			NP_001317215.1
DUT	NM_001948.4	c.293-333C>T		intron_variant			NP_001939.1
DUT	NM_001025249.1	c.224-333C>T		intron_variant			NP_001020420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUT	ENST00000331200.8	c.557-333C>T		intron_variant		1	NM_001025248.2	ENSP00000370376.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81753 AN: 151994 Hom.: 28329 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81730 AN: 152112 Hom.: 28323 Cov.: 32 AF XY: 0.535 AC XY: 39773 AN XY: 74356

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.561

Alfa AF: 0.712 Hom.: 86684

Bravo AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.73

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: rs11637235; hg19: chr15-48633153;