rs9567986

Positions:

• chr13-48044034-C-T

Variant summary

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

The NM_018283.4(NUDT15):​c.356-1626C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,018 control chromosomes in the GnomAD database, including 9,380 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 0.34 (9380 hom., cov: 32)
• Consequence: NUDT15 NM_018283.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDT15	NM_018283.4	c.356-1626C>T		intron_variant		ENST00000258662.3
NUDT15	NR_136687.2	n.377-1626C>T		intron_variant, non_coding_transcript_variant
NUDT15	NR_136688.2	n.377-1626C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDT15	ENST00000258662.3	c.356-1626C>T		intron_variant		1	NM_018283.4	P1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51952 AN: 151900 Hom.: 9348 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.342 AC: 52038 AN: 152018 Hom.: 9380 Cov.: 32 AF XY: 0.345 AC XY: 25652 AN XY: 74310

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.339

Alfa AF: 0.329 Hom.: 2999

Bravo AF: 0.351

Asia WGS AF: 0.428 AC: 1489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.33

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: rs9567986; hg19: chr13-48618170;