13-48045806-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018283.4(NUDT15):​c.*7G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000568 in 1,408,596 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: 0.0000057 (0 hom.)
• Consequence: NUDT15 NM_018283.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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>C		3_prime_UTR	Exon 3 of 3	NP_060753.1	Q9NV35
	NUDT15	NR_136687.2		n.523G>C		non_coding_transcript_exon	Exon 3 of 5
	NUDT15	NR_136688.2		n.516+7G>C		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>C		3_prime_UTR	Exon 3 of 3	ENSP00000258662.1	Q9NV35
	NUDT15	ENST00000875703.1		c.*7G>C		3_prime_UTR	Exon 3 of 4	ENSP00000545762.1
	NUDT15	ENST00000913137.1		c.*7G>C		3_prime_UTR	Exon 3 of 4	ENSP00000583196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000969 AC: 2 AN: 206292 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000201

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000568 AC: 8 AN: 1408596 Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2 AN XY: 699372

African (AFR) AF: 0.00 AC: 0 AN: 30090

American (AMR) AF: 0.00 AC: 0 AN: 32996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24148

East Asian (EAS) AF: 0.00 AC: 0 AN: 36704

South Asian (SAS) AF: 0.00 AC: 0 AN: 77756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5414

European-Non Finnish (NFE) AF: 0.00000733 AC: 8 AN: 1091092

Other (OTH) AF: 0.00 AC: 0 AN: 57942

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.35
PhyloP100		-0.18

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;