Variant 13-48045806-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_018283.4(NUDT15):c.*7G>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 0.0649 in 1,559,978 control chromosomes in the GnomAD database, including 3,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.055 ( 349 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3491 hom. )

Consequence

NUDT15
NM_018283.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.178

Variant links:

Genes affected

NUDT15 (HGNC:23063): (nudix hydrolase 15) This gene encodes an enzyme that belongs to the Nudix hydrolase superfamily. Members of this superfamily catalyze the hydrolysis of nucleoside diphosphates, including substrates like 8-oxo-dGTP, which are a result of oxidative damage, and can induce base mispairing during DNA replication, causing transversions. The encoded enzyme is a negative regulator of thiopurine activation and toxicity. Mutations in this gene result in poor metabolism of thiopurines, and are associated with thiopurine-induced early leukopenia. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Apr 2016]

NUDT15 links:

NUDT15 (HGNC:):

NUDT15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 13-48045806-G-A is Benign according to our data. Variant chr13-48045806-G-A is described in ClinVar as [Benign]. Clinvar id is 3055414.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
NUDT15	NM_018283.4 linkuse as main transcript	c.*7G>A	3_prime_UTR_variant	3/3	ENST00000258662.3	NP_060753.1	Q9NV35
NUDT15	NR_136687.2 linkuse as main transcript	n.523G>A	non_coding_transcript_exon_variant	3/5
NUDT15	NR_136688.2 linkuse as main transcript	n.516+7G>A	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT15	ENST00000258662.3 linkuse as main transcript	c.*7G>A		3_prime_UTR_variant	3/3	1	NM_018283.4	ENSP00000258662.1		Q9NV35

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8442

AN:

152058

Hom.:

346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0467

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.0513

GnomAD3 exomes

AF:

0.0695

AC:

14340

AN:

206292

Hom.:

742

AF XY:

0.0664

AC XY:

7507

AN XY:

113044

show subpopulations

Gnomad AFR exome

AF:

0.0122

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.0533

Gnomad EAS exome

AF:

0.0000707

Gnomad SAS exome

AF:

0.0367

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0689

Gnomad OTH exome

AF:

0.0713

GnomAD4 exome

AF:

0.0659

AC:

92729

AN:

1407800

Hom.:

3491

Cov.:

AF XY:

0.0648

AC XY:

45276

AN XY:

698966

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.000763

Gnomad4 SAS exome

AF:

0.0363

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0682

Gnomad4 OTH exome

AF:

0.0609

GnomAD4 genome

AF:

0.0555

AC:

8440

AN:

152178

Hom.:

349

Cov.:

AF XY:

0.0586

AC XY:

4359

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0467

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0303

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0661

Gnomad4 OTH

AF:

0.0508

Alfa

AF:

0.0602

Hom.:

189

Bravo

AF:

0.0549

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NUDT15-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.31

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over