7-2251050-C-T

Variant names:

• chr7-2251050-C-T
• rs1062492
• NM_002452.4:c.*49C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002452.4. 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
	NUDT1	NM_002452.4	MANE Select	c.*49C>T		3_prime_UTR	Exon 4 of 4	NP_002443.3
	NUDT1	NM_198949.2		c.*49C>T		3_prime_UTR	Exon 5 of 5	NP_945187.1	P36639-2
	NUDT1	NM_198952.2		c.*49C>T		3_prime_UTR	Exon 5 of 5	NP_945190.1	P36639-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUDT1	ENST00000356714.6	TSL:1 MANE Select	c.*49C>T		3_prime_UTR	Exon 4 of 4	ENSP00000349148.1	P36639-4
	NUDT1	ENST00000343985.8	TSL:1	c.*49C>T		3_prime_UTR	Exon 4 of 4	ENSP00000339503.4	P36639-2
	NUDT1	ENST00000397048.5	TSL:1	c.*49C>T		3_prime_UTR	Exon 5 of 5	ENSP00000380241.1	P36639-2

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

GnomAD2 exomes AF: 0.170 AC: 42283 AN: 248864 AF XY: 0.173

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 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

African (AFR) AF: 0.0550 AC: 1816 AN: 33016

American (AMR) AF: 0.188 AC: 8394 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6208 AN: 26002

East Asian (EAS) AF: 0.0514 AC: 2034 AN: 39562

South Asian (SAS) AF: 0.186 AC: 15885 AN: 85618

European-Finnish (FIN) AF: 0.152 AC: 7948 AN: 52170

Middle Eastern (MID) AF: 0.261 AC: 1399 AN: 5360

European-Non Finnish (NFE) AF: 0.182 AC: 199293 AN: 1093912

Other (OTH) AF: 0.178 AC: 10588 AN: 59624

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

African (AFR) AF: 0.0603 AC: 2498 AN: 41454

American (AMR) AF: 0.200 AC: 3058 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3472

East Asian (EAS) AF: 0.0647 AC: 333 AN: 5150

South Asian (SAS) AF: 0.203 AC: 976 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1540 AN: 10574

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12229 AN: 67956

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.171 Hom.: 1541

Bravo AF: 0.147

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.037
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: rs1062492; hg19: chr7-2290685;