7-2251050-C-T

Position:

• chr7-2251050-C-T

Variant summary

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

The NM_002452.4(NUDT1):​c.*49C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,591,936 control chromosomes in the GnomAD database, including 25,184 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 0.15 (1869 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23315 hom.)
• Consequence: NUDT1 NM_002452.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

Genes affected

NUDT1 (HGNC:8048): (nudix hydrolase 1) Misincorporation of oxidized nucleoside triphosphates into DNA/RNA during replication and transcription can cause mutations that may result in carcinogenesis or neurodegeneration. The protein encoded by this gene is an enzyme that hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates, thereby preventing misincorporation. The encoded protein is localized mainly in the cytoplasm, with some in the mitochondria, suggesting that it is involved in the sanitization of nucleotide pools both for nuclear and mitochondrial genomes. Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional variants have been observed, but their full-length natures have not been determined. A rare single-nucleotide polymorphism that results in the production of an additional, longer isoform (p26) has been described. [provided by RefSeq, Dec 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUDT1	NM_002452.4	c.*49C>T		3_prime_UTR_variant	4/4	ENST00000356714.6	NP_002443.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDT1	ENST00000356714.6	c.*49C>T		3_prime_UTR_variant	4/4	1	NM_002452.4	ENSP00000349148	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22097 AN: 151910 Hom.: 1861 Cov.: 32

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.170 AC: 42283 AN: 248864 Hom.: 3992 AF XY: 0.173 AC XY: 23345 AN XY: 134914

Gnomad AFR exome AF: 0.0581

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.0600

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.176 AC: 253565 AN: 1439914 Hom.: 23315 Cov.: 27 AF XY: 0.177 AC XY: 126799 AN XY: 717652

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.0514

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.146 AC: 22126 AN: 152022 Hom.: 1869 Cov.: 32 AF XY: 0.145 AC XY: 10769 AN XY: 74296

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0647

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.184

Alfa AF: 0.171 Hom.: 1414

Bravo AF: 0.147

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.69

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: rs1062492; hg19: chr7-2290685;