13-48045806-G-A

Variant names:

• chr13-48045806-G-A
• rs61973267
• NM_018283.4:c.*7G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.178
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018283.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT15	NM_018283.4	MANE Select	c.*7G>A		3_prime_UTR	Exon 3 of 3	NP_060753.1	Q9NV35
	NUDT15	NR_136687.2		n.523G>A		non_coding_transcript_exon	Exon 3 of 5
	NUDT15	NR_136688.2		n.516+7G>A		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT15	ENST00000258662.3	TSL:1 MANE Select	c.*7G>A		3_prime_UTR	Exon 3 of 3	ENSP00000258662.1	Q9NV35
	NUDT15	ENST00000875703.1		c.*7G>A		3_prime_UTR	Exon 3 of 4	ENSP00000545762.1
	NUDT15	ENST00000913137.1		c.*7G>A		3_prime_UTR	Exon 3 of 4	ENSP00000583196.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8442 AN: 152058 Hom.: 346 Cov.: 32

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

GnomAD2 exomes AF: 0.0695 AC: 14340 AN: 206292 AF XY: 0.0664

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 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.: 30 AF XY: 0.0648 AC XY: 45276 AN XY: 698966

African (AFR) AF: 0.0107 AC: 323 AN: 30088

American (AMR) AF: 0.146 AC: 4800 AN: 32952

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 1245 AN: 24136

East Asian (EAS) AF: 0.000763 AC: 28 AN: 36704

South Asian (SAS) AF: 0.0363 AC: 2824 AN: 77740

European-Finnish (FIN) AF: 0.104 AC: 5440 AN: 52444

Middle Eastern (MID) AF: 0.0301 AC: 163 AN: 5414

European-Non Finnish (NFE) AF: 0.0682 AC: 74377 AN: 1090394

Other (OTH) AF: 0.0609 AC: 3529 AN: 57928

GnomAD4 genome AF: 0.0555 AC: 8440 AN: 152178 Hom.: 349 Cov.: 32 AF XY: 0.0586 AC XY: 4359 AN XY: 74398

African (AFR) AF: 0.0142 AC: 589 AN: 41530

American (AMR) AF: 0.110 AC: 1675 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0303 AC: 146 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1159 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4493 AN: 67988

Other (OTH) AF: 0.0508 AC: 107 AN: 2108

Alfa AF: 0.0602 Hom.: 189

Bravo AF: 0.0549

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NUDT15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.31
DANN	Benign	0.50
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs61973267; hg19: chr13-48619942;